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Letter to the Editor
Cardiovascular Research Convergence 2022
The Cardiovascular Research Convergence meetings came into
existence years back when cardiac treatment was established
and the need for basic scientists came in the role for better
diagnosis to rule the nitty gritty at the molecular level during
treatment of cardiac patients. This was the 11th successful
convergence organized in CSIR-Indian Institute of Chemical
Biology, Kolkata, in collaboration with the Department of
Cardiology, AIIMS, New Delhi, on June 25, 2022, Saturday.
There was active participation from different institutes around
the country, i.e., CSIR Institute of Genomics and Integrative
Biology; Department of Cardiology, AIIMS, New Delhi; Indian
Institute of Chemical Technology, Hyderabad; Centre for
Cellular and Molecular Biology, Hyderabad; and Department
of Pharmacology and Toxicology, National Institute of
Pharmaceutical Education and Research, Guwahati. The
Convergence topics were planned according to the various
shortcomings in cardiac patients, as we are witnessing a
significant rise every year. There were three categories of
presentation: (1) Oral Presentation for Prof. S. K. Maulik
Award (Basic Science); (2) Oral Presentation for Prof. Balram
Bhargava Award (Clinical Science); (3) Poster Presentation.
The active participation of students from various institutes was
seen during the presentation.
The Convergence maintained the legacy of providing new
horizons to both Clinical and Basic scientists, by exchanging
various ideas and developing future collaborations. Hoping to
continue the standard of Convergence by widening the network
all over the country for a better future in cardiac treatment
[Figure 1 and 2].
Winners of Basic Science: Prof. S. K. Maulik
Award
1a. Understanding the Pathophysiological Implications of
Dysregulated Cholesterol Homeostasis
Aleepta Guha Ray, Kamalika Roy Choudhury, Devasmita Chakravarty, Vivek
Chander, Khawer N. Siddiqui1, Aditya Konar, Arun Bandyopadhyay
Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology,
1
Division of Cardiac Research, Ruby General Hospital, Kolkata, West Bengal, India
E-mail: aleeptagr@gmail.com
The efflux of excess cholesterol in macrophages, primarily
mediated by ABCA1, is essential for alleviating atherosclerosis,
but the role of secondary transporters has not been explored
in detail. We report, for the first time, the inverse relationship
between plasma levels of ABCA1 and ABCA5 in high
cholesterol diet-fed mouse models of atherosclerosis (ApoE−/−)
and hyperlipidemia (PPARα−/−) and their clinical correlation in
human samples. Taking our study further, we have performed
a multiomic study to understand the changes in the plaque
macrophages subpopulation in response to statin therapy and the
© 2022 Journal of the Practice of Cardiovascular Sciences | Published by Wolters Kluwer - Medknow
resulting cytokines and chemokines profile, which contributes to
the healing phenotype. Surprisingly, an increase of inflammatory
macrophages is observed in response to a significant lowering of
cholesterol build-up which we have characterized further. Our
study indicates that upregulation of apoptosis-inducing factors
seems to be necessary for efferocytosis in the plaque and increase
in reverse cholesterol transport.
Keywords: macrophages, cytokines, apoptosis
1b. Peptidoglycan Recognition Protein 2 Activates NOD2-
NFκβ Inflammatory Axis in Atherosclerosis
Pratitusti Basu, Apabrita Ayan Das, Khawer N. Siddiqui1, Prakash C.
Mandal2, Arun Bandyopadhyay
Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical
Biology, 1Department of Cardiology, Apollo Gleneagles Hospital, 2Department of
Cardiology, Ruby General Hospital, Kolkata, West Bengal, India
E-mail: prati07basu@gmail.com
Inflammation is one of the major drivers of atherogenesis. The
inflammation caused by atherosclerosis does not only act locally,
but the manifestation can also be found in the entire circulatory
system. Hence, the proteins that show altered expression in
plasma, in the background of coronary artery disease, can
provide an insight into the mediators that may have an interesting
role in plaque development and progression. Plasma-soluble
peptidoglycan recognition protein 2 (PGLYRP2) is reported
to be associated with chronic inflammation by recognizing
the peptidoglycan component of bacterial cell membrane and
cleaving it with the C-terminal amidase domain. The correlation
of elevated levels of plasma PGLYRP2 with the severity of
coronary artery disease raises interest to understand the role of
the protein in atherosclerosis. In this study, we report, for the first
time, that plasma-soluble PGLYRP2 interacts with the receptor
NOD2, present on the macrophage cell membrane at the site
of the lesion. The N-terminal domain of the protein PGLYRP2
directly binds to NOD2 on the surface of macrophages and
activates NOD2-RIP2-NFκβ cascade that ultimately promotes
further inflammation. We showed that treatment with human
recombinant PGLYRP2 protein to the macrophages in vitro
results in increased secretion of proinflammatory cytokines
(tumor necrosis factor-α, interleukin 1 beta and interleukin 8).
In vivo study using atherosclerosis mice model showed elevated
plasma PGLYRP2 along with increased TNF-α level associated
with advanced plaque in the coronary artery, indicating the
contribution of PGLYRP2-NOD2 interaction promoting
inflammation. Here, we demonstrate that increased plasma-
soluble PGLYRP2 interacts with NOD2 and activates the
downstream inflammatory pathway that accelerates the
inflammation toward an unresolved state that might eventually
promote persistent chronic inflammation.
Keywords: Peptidoglycan, inflammation, plaque
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Letter to the Editor
Figure 1: Inauguration ceremony.
1c. Uncovering Sex-Specific Differential Molecular
Mechanisms in Cerebrovascular Incidents using Mouse
Mild-Stroke Model
Mydhili Radhakrishnan1,2, Kalyani Soren1,2, Vincy Vijay1,2, Arvind Kumar2,3,
Sumana Chakravarty1,2
1
Department of Applied Biology, Indian Institute of Chemical Technology,
3
Centre for Cellular and Molecular Biology, Hyderabad, Telangana, 2Academy of
Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, India
E-mail: mydhilikrishnan@gmail.com
Cerebral stroke is one of the leading causes of death and
disability worldwide. Therapeutic interventions to minimize
ischemia-induced neural damage are limited due to poor
understanding of molecular mechanisms of the complex
pathophysiology due to a dearth of appropriate animal
model. The most popular rodent cerebral stroke model is
middle cerebral artery occlusion model, although 25% of
stroke cases are due to the internal carotid artery occlusion
(ICAO). Moreover, earlier studies showed that gender
plays an important role in regulating pathophysiological
changes in cerebral stroke. Sex difference seems to reflect a
major influence not only on stroke vulnerability but also on
poststroke cellular and molecular event. To address this, we
have used recently developed ICAO mouse (CD1) model
considerably close to human cerebrovascular incidents, to
explore the sequential molecular events, including epigenetic
changes during neural damage and repair in both the sexes.
Various behavioral paradigms were employed to assess ICAO-
induced deficits in motor/locomotor abilities such as NDS,
rotarod test, grip strength, and open field tests at different time
points up to 7 days of post-ICAO. The results revealed that
females recover faster than males. By investigating regulatory
molecular mechanisms, as well as triggering recovery
mechanisms individually, we could observe interesting sex-
specific patterns in the onset of epigenetic, inflammatory, and
mitochondrial activity pathways. Interestingly, in females,
the post-ICAO recovery mechanism appears to be triggered
earlier than in males. Overall results clearly indicated that
the differential sex-specific recovery mechanism might play
a key role in regulating the susceptibility to cerebrovascular
diseases [Figure 3].
Keywords: Therapeutic, ischemia, cerebovascular
118 Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
Figure 2: Session during Convergence.
Winner of Clinical Science Prof. Balram
Bhargava Award
2a. Common Promoter Variants in the Matrix
Metalloproteinase 8 Gene Contribute to Hypertension in
Human Populations
Sakthisree Maghajothi, Lakshmi Subramanian, Preethi Mani, Mrityunjay
Singh1, Dhanya R. Iyer, Saurabh Sharma2, Madhu Khullar2, Suma M. Victor3,
Shailendra Asthana1, Ajit S. Mullasari3, Nitish R. Mahapatra
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences,
Indian Institute of Technology Madras, 4Institute of Cardiovascular Diseases,
Madras Medical Mission, Chennai, 1Translational Health Science and
Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana,
2
Department of Experimental Medicine and Biotechnology, Postgraduate Institute
of Medical Education and Research, Chandigarh, India
E-mail: sakthi.m.13@gmail.com
Altered matrix metalloproteinase 8 (MMP8, collagenase 2)
levels are associated with increased risk of cardiovascular
diseases (CVDs). MMP8 degrades matrix proteins such as
collagen through its proteolytic activity. Disturbed collagen
turn-over in the blood vessels leads to hypertension, an
independent predictor of CVDs. However, the contribution
of MMP8 to hypertension remains poorly understood. Hence,
we aimed to investigate the association of MMP8 regulatory
single-nucleotide polymorphisms (SNPs) with hypertension in
Indian populations. We genotyped 2565 unrelated individuals
for the promoter SNPs in MMP8 gene and identified 4 SNPs
in the upstream ~1.3 kb promoter region of MMP8: -763A/T
(rs35308160), -799C/T (rs11225395), -815G/T (rs17099451),
and -1089A/G (rs17099452); these SNPs form three major
haplotypes. Hap3 (haplotype comprising variant allele of all
4 SNPs) displayed significant association with hypertension
(Chennai: odds ratio [OR] = 1.47, 95% confidence interval
[CI] = 1.16–1.86, P = 2 × 10−3; Chandigarh: OR = 1.85,
95% CI = 1.21–2.81, P = 4 × 10−3) and exhibited elevated
Systolic blood pressure (SBP), Diastolic blood pressure
(DBP), and mean arterial pressure (MAP) compared to wild-
type haplotype (Hap1). Hap3 exhibited diminished promoter
activity compared to the wild-type haplotype. In line with
the in silico predictions and molecular dynamics analysis,
co-transfection of the Hap3 with NF-κB expression plasmid
displayed a diminished enhancement in the reporter activity
compared to wild-type haplotype. Moreover, Hap3 also showed
weak response to TNF-α treatment, which could be attributed
to the weaker binding of NF-κB to Hap3. Plasma MMP8
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Letter to the Editor

Figure 3: Uncovering sex-specific differential molecular mechanisms in cerebrovascular incidents using mouse mild-stroke model. ICAO: Internal
carotid artery occlusion.

Figure 4: Targeted placental metabolomic profiling to unravel the disease-specific biomarkers in GH. GH: Gestational hypertension, LC-MS: Liquid
chromatography–mass spectrometry.

level of Hap3 heterozygous genotype individuals was lower,
whereas the endothelial dysfunction markers (endothelin-1
and von Willebrand factor (vWF)) were elevated compared to
wild-type individuals. Our findings suggest that altered MMP8
expression in individual’s harboring these MMP8 promoter
variants may cause differential response to inflammatory
queues and contribute to the development of hypertension.
Keywords: heterozygous genotype, single-nucleotide
polymorphisms, haplotype
2b. Inflammatory Cardiomyopathy: Validating a Diagnostic
Algorithm Combining Biomarkers, Magnetic Resonance
Imaging, and Somatostatin Receptor-Based Positron
Emission Tomography/Computed Tomography
Kavita Kumari, Shivani Vashista, Deepika Jindal, Santoshi Sahani, Sandeep
Seth, R Narang
Department of Cardiology, AIIMS, New Delhi, India
E-mail: kavitavermaaiims@gmail.com
Objective: Inflammatory cardiomyopathy, majorly caused by
viral infections, autoimmune diseases, hypersensitivity, and
sarcoidosis, is a primary cause of heart failure in India. It is
estimated that about one-third of myocarditis patients develop
dialated cardiomyopathy (DCM). With the help of imaging
techniques like Magnetic resonance (MRI) and positron emission
tomography resulted in better diagnosis of Myocarditis. This
study is an attempt to create a combined diagnostic score
based on the above information, to diagnose inflammatory
cardiomyopathy. Methods: A total of 100 patients with
inflammatory cardiomyopathy have been recruited. Investigation
includes echo, MRI, nuclear scans, and Endomyocardial biopsy
(EMBx). Information from all this was combined to create a
diagnostic score, and this was then tested on the recruited patient
cohort. Results: The components of the score include viral
prodrome, inflammation and cardiac stress, and injury biomarkers
such as C reactive Protein (CRP), Brain natriuretic peptide
(BNP), and troponins. Electrocardiographic changes and imaging
by MRI or Dotanoc were also scored. EMBx was scored. Most
parameters if positive were given a score of 2, and a total score
of 7 was considered, suggestive of probable myocarditis. This
score was applied to the 100 patients for validation and accuracy
checking. Conclusion: A diagnostic score has been created for
myocarditis and validated on 100 patients. Wider application to
more patients will show the robustness of this score.
Keywords: cardiomyopathy, Electrocardiographic,
hypersensitivity
2c. Targeted Placental Metabolomic Profiling to Unravel the
Disease-Specific Biomarkers in Gestational Hypertension
Bincy Varghese, Soumya Reddy, Aishwarya Jala1, Roshan M. Borkar1, Ramu
Adela

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Letter to the Editor

Figure 5: Pregastational diabetes alters metabolic flexibility in neonatal heart: Impact on amino acid and fat metabolism.

Figure 6: Modulating Nrf2/HO-1 and TGF-β1/Smad2/3 signaling cascade ameliorates TAC-induced cardiac remodeling in mice.

Departments of Pharmacy Practice and 1Pharmaceutical Analysis, National
Institute of Pharmaceutical Education and Research, Guwahati, Assam, India
E-mail: binzvarghese90@gmail.com
Women with a history of hypertensive disorders during
pregnancy have a 2–3 folds greater risk of cardiovascular
disease in their later life. Gestational hypertension (GH)
accounts for about 3%–10% of maternal-fetal morbidity
and mortality, worldwide. Recent advances in the field of
high-throughput omic techniques contributed significantly to
identifying potential therapeutic targets and biomarkers for
various pathological conditions. Identification of placental
metabolic adaptations during pregnancy may help in getting
a deeper understanding of maternal, placental, and fetal
health, especially in pathological pregnancies such as GH.
We have determined the placental metabolic alterations of
healthy pregnant (n = 20) and GH patients (n = 20) using a
targeted metabolomic approach. The signature metabolites
were extracted using univariate and multivariate analyses.
Statistical analysis showed a total of 98 significantly altered
metabolites, with 65 downregulated and 33 upregulated ones.
The major pathways affected were the purine, amino acid, and
aminoacyl-tRNA biosynthesis. Receiver operator characteristic
curve analysis showed five significant metabolites (spermine,
inosine, sarcosine, alanine, and eicosatetraenoic acid) that can
discriminate GH than the hypertension (HP) with area under
the curve, area under the receiver operating characteristics
(AUROC) ≥0.90, with higher sensitivity and specificity. Overall,
this is the first attempt to unravel tissue metabolomic aberrations
in Hypertensive Disorders in Pregnancy (HDP) patients in the
Indian population. These results may add to the knowledge of
the molecular mechanisms behind the development of these
progressive diseases, which might aid in better understanding
of disease pathophysiology and monitoring therapeutic response
in severe hypertensive patients in the future [Figure 4].
Keywords: Biomarkers, gestational hypertension, metabolomics,
pregnancy
Poster Presentation Award
3a. Regulation of Peroxiredoxin-3 Gene Expression
by Transcription Factors Specificity Protein 1, cAMP
Response Element–Binding Protein, and Nuclear Factor
Kappa-Light-Chain-Enhancer of Activated B Cells in
Diabetic Cardiomyopathy
Silpa Arkat, Rohini Dhat1, Sandhya L. Sitasawad1, Nitish R. Mahapatra

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Letter to the Editor

b
Figure 7: (a) DBH inhibition can reduce the otherwise vasostimulatory effects of norepinephrine (noradrenaline) and epinephrine (adrenaline). (b)
Representation of the events involved in inhibitor designing and testing. DBH: Dopamine beta hydroxylase.

Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences,
Indian Institute of Technology Madras, Chennai, Tamil Nadu, 2National Centre
for Cell Science, Savitribai Phule Pune University Campus, Pune, Maharashtra,
India
E-mail: silpa.knlarkat@gmail.com
Background: Diabetes contributes to a distinct form of
heart muscle disorder known as diabetic cardiomyopathy
(DCM), which profoundly increases the risk of heart failure.
Mitochondrial oxidative stress is a major contributor to the
progression of DCM. Peroxiredoxin-3 (Prx-3), a mitochondrial
antioxidant protein, is crucial for regulating hydrogen peroxide
levels in most cells. In fact, a reduced level of Prx-3 has been
linked to various cardiovascular diseases (viz., myocardial
infarction/DCM/dilated cardiomyopathy), and overexpression
of Prx-3 prevents the above pathological conditions in various
animal models. However, the transcriptional regulation of Prx-
3 is poorly understood. In this study, we aim to identify the
transcription factors (TFs) governing Prx-3 gene expression
under basal and DCM conditions. Methods: Systematic in
silico TF prediction tools and experimental analyses (promoter-
reporter, co-transfection, and chromatin immunoprecipitation
[ChIP] assays) were used to identify potential TFs that regulate

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Figure 8: Allyl Methyl Sulfide Attenuating Platelet Activation in Diabetes
by Inhibiting the Metabolism of Arachidonic Acid Pathway.
Prx-3 gene expression. Results: To identify the core promoter
region of Prx-3, varying lengths of rat Prx-3 promoter (−1200,
−457, −251, −190, −134 bp to +20 bp) were polymerase chain
reaction (PCR)-amplified and cloned into promoter-less pGL4.2
basic vector. Transfection of these deletion constructs into HEK-
293, H9c2, N2a, E9, and Huh-7 cells shows the highest promoter
activity in the case of −190 bp construct. Systematic in silico
analysis of the −190/+20 bp promoter domain revealed putative
binding sites for specificity protein 1 (Sp1), cAMP response
element–binding protein (CREB), and nuclear factor kappa-
light-chain-enhancer of activated B cells (NF-κB). Consistently,
co-transfection of the −190/+20 bp construct with Sp1/CREB
diminished and NF-κB augmented the Prx3 promoter-reporter
activity, mRNA, and protein levels. Co-transfection of Sp1/
CREB/NF-κB shRNA plasmids showed promoter-reporter
activity, mRNA, and protein levels, consistent with these results.
Furthermore, in vivo interaction of Sp1, CREB, and NF-κB with
the rPrx-3 promoter in the context of chromatin was confirmed
by ChIP assays. High-glucose treatment of H9c2 cells and
streptozotocin (STZ)-treated diabetic rats showed an inverse
correlation between rPrx-3 and Sp1/CREB levels. Microarray
data from GEO Dataset also demonstrated similar trends
between rPrx-3 and Sp1/CREB levels in the hearts of control and
STZ-induced diabetic rats. Thus, Sp1/CREB/NF-κB emerges as
important regulators of rPrx-3 gene expression in DCM.
Keywords: Co-transfection, streptozotocin, geneexpression
3b. Reduction in PTEN-Mediated Apoptosis Is Counteracted
by Calpain-1 Regulated Autophagy in Cardiac Hypertrophy
of Peroxisome Proliferator-Activated Receptor alpha−/−
Mice
Ritu Kumari, Aleepta Guha Ray, Dibyanti Mukherjee, Dipak Kar, Aditya Konar,
Arun Bandyopadhyay1
122 Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
Figure 9: Graphical representation of cardioprotection by terbium
hydroxide nanorods.
1
Department of Cell Biology and Physiology, CSIR- Indian Institute of Chemical
Biology, Kolkata, West Bengal, India
E-mail: rituk2906@gmail.com
Cardiac hypertrophy is characterized by an increase in the
size of the cardiomyocytes, which is initially triggered as
an adaptive response due to various kinds of stimuli but
ultimately becomes maladaptive with chronic exposure.
Peroxisome proliferator-activated receptor alpha (PPARα),
which is critical for mitochondrial biogenesis and fatty acid
oxidation, is known to be downregulated in hypertrophied
cardiomyocytes. Yet, the role of PPARα in cardiomyocyte
death is largely unknown. To assess the role of PPARα in
chronic hypertrophy, isoproterenol, a β-adrenergic receptor
agonist, was administered in PPARα knock-out (PPARα−/−)
mice for 2 weeks, and hypertrophy-associated changes
in cardiac tissues were observed. Proteomic analysis
using Orbitrap mass spectrometer revealed an unexpected
downregulation of apoptotic markers, Annexin V and p53.
The study revealed a significant downregulation of apoptosis
regulator, PTEN, along with other apoptosis markers such as
p53, caspase 9, and c-PARP Poly (ADP-ribose) polymerase.
The autophagy markers were upregulated in PPAR α−/−mice,
indicating an upsurge in autophagy. The results were further
validated in vitro using NRVMs and H9C2 cell line by
blocking PPARα that resulting in enhanced autophagosome
formation upon hypertrophic stimulation. The results
demonstrate that in the absence of PPARα, apoptotic pathway
is inhibited while autophagy is enhanced. The data suggest
that PPARα signaling might act as a molecular switch between
apoptosis and autophagy, thereby playing a critical role in
adaptive process of cardiac hypertrophy.
Keywords: Autophagy, biogenesis, autophagosome
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Letter to the Editor
3c. Identification of Adamts4, a Matrix Metalloproteinase
as a Novel Cardiac Injury Biomarker with Implications in
Patients with Cardiac Injury
Riffat Khanam, Santanu Charaborty
Department of Life Sciences, Presidency University, Kolkata, West Bengal, India
E-mail: riffat.rs@presiuniv.ac.in
Pathological cardiac remodeling as an aftermath of a severe
cardiac injury can lead to ventricular dysfunction and
subsequent heart failure. Our study focuses on Adamts4, a
matrix metalloproteinase (MMP) and extracellular matrix
(ECM) marker following cardiac injury. Our studies show that
the widespread prevalence of Adamts4 throughout chamber
myocardium in the embryonic stages severely wanes and
is only restricted to the edge of the IVS but reactivation of
Adamts4 in the left ventricle of chamber myocardium post-
myocardial infarction (MI) induction in an adult murine model
Figure 10: Aloin inhibits cardiac hypertrophy by upregulating nuclear
factor erythroid 2–related factor-2-mediated antioxidant responses and
alleviating TGF-β/Smad2/3 signaling axis.
Figure 11: Effect of Vitamin D Supplementation in Cardiovascular Disease Prevention in Type 2 Diabetes Patients: Focusing on Platelet-Mediated
Inflammation.
Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
is observed, and interestingly, the expression of Adamts4
co-localized with cardiomyocytes. To further decipher the
signaling, Adamts4 induction was induced by hypoxia and
reactive oxygen species (ROS) stress treatment in H9c2, a
rat cardiomyocyte cell line. In response to both the stress
conditions, Admats4 expression along with Tgf-β, α-SMA,
Col-III, and periostin was significantly enhanced as validated
by Western Blot, IF, and qPCR data. Moreover, Tgf-β inhibition
by ALKI treatment shows Adamts4 downregulation and
subsequent repression of the above-mentioned ECM and
fibrosis markers. However, Adamts4 loss of function by
Adamts4-specific siRNA transfection showed no significant
change in the expression of Tgf, indicating Tgf-β–dependent
Adamts4 functioning. Finally, Adamts4 and α-SMA expression
was studied in clinical samples with a history of MI Anterior
wall myocardial infarction (AWMI), Inferior wall myocardial
infarction (IWMI) and dilated cardiomyopathy where the
expression of Adamts4 was significantly elevated as quantified
by Western blot for Adamts4 and α-SMA in addition to
Adamts4-specific ELISA. Our work highlights the emerging
role of Adamts4 as an alternative cardiac injury marker in
addition to the routinely assessed cardiac biomarkers.
Keywords: Matrix Metalloproteinase, Adamts4, siRNA
Various Other Studies Presented in
Cardiovascular Research Convergence 2022
4a. Role of Bmp2 in Regulating Cardiac Remodelling
Postendoplasmic Reticulum Stress
Shreya Das, Santanu Chakraborty1, Arunima Sengupta
Department of Life Science and Biotechnology, Jadavpur University,
1
Department of Life Sciences, Presidency University, Kolkata, West Bengal,
India
E-mail: arunimasengupta2013@gmail.com
Adult cardiomyocytes in mammals fail to retain the proliferative
capacity exhibited by neonatal cardiomyocytes before birth. An
insult to endoplasmic reticulum (ER) machinery often results in
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Letter to the Editor
the development of ER stress-mediated cardiomyopathy. There
is a very fine balance between pro-survival and pro-apoptosis
during ER stress-induced cardiomyopathy. In this study, we
investigate the role of Bmp2 as a potential marker in imparting
this pro-survival response in the milieu of ER stress-induced
cardiomyopathy. We observed increased expression of Tbx20
and Bmp2 with increased cardiomyocyte proliferation and
decreased apoptosis upon ER stress induction. Their expression
decreased with increased intensity and duration of ER stress
with concomitant increase in cardiomyocyte apoptosis,
hypertrophy, and fibrosis. Administration of recombinant Bmp2
protein resulted in restoration of cardiomyocyte proliferation
even during chronic ER stress in vitro. Knockdown of Tbx20
and use of Bmp2 inhibitor noggin showed Bmp2 to be
downstream of Tbx20. In mice, sustained ER stress resulted
in drastic increase in Bmp2 expression, which is attributed
to the heterogeneity of heart tissue. Sustained ER stress also
results in increased inflammation which in turn increases Bmp2
expression. Increased Bmp2 in turn causes augmentation of
pro-inflammatory phenotype in the endothelial cell following
injury. Thus, Bmp2 imparts protection post-ER stress by
augmenting cardiomyocyte proliferation; however, its drastic
increase during chronic ER stress is due to factors such as
inflammation and other cell types of the heart, thus making it
a suitable candidate for a novel biomarker for early detection
of ER stress-mediated cardiomyopathy.
Keywords: endoplasmic reticulum, Tbx20 and Bmp2,
heterogeneity
4b. Transcriptional Regulation of Adult Cardiac Fibrosis
Process
Ipshit Dey, Santanu Chakraborty
Heart Development and Disease Laboratory, Department of Life Sciences,
Presidency University, Kolkata, West Bengal, India
E-mail: ipshit.rs@presiuniv.ac.in
Cardiovascular disease is one of the main causes of death
worldwide, and nearly all etiologies of cardiovascular disease
are associated with activation of cardiac fibroblasts. After adult
cardiac injuries such as myocardial infarction, these resident
cardiac fibroblasts proliferated and differentiated into activated
myofibroblasts with the production of excessive amount of
fibrous collagens and subsequent fibrotic scar formation.
This pathological myocardial remodeling associated with
cardiomyocyte hypertrophy and death leads to overall cardiac
dysfunction and progression toward heart failure. Despite the
prevalence of cardiac fibrosis downstream of many cardiac
injuries, we have a little understanding of its transcriptional
regulation in vivo. T-box transcription factor, Tbx20 has a
role in heart development and also plays an important role in
embryonic, fetal, and neonatal cardiomyocyte proliferation
and cardiac chamber maturation, but its role in cardiac fibrosis
process is unknown. Here, we have generated a cardiac fibrosis
model in adult male rats by isoproterenol treatment. Treatment
of isoproterenol induces hypertrophic response along with
increased expression of activated myofibroblasts and collagen
124 Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
type III associated with active fibrosis. To our surprise,
preliminary experiment also detected an increased number
of Tbx20 positive-activated myofibroblasts in isoproterenol-
treated adult hearts. Overall, this study, for the first time,
explores the Tbx20 function in adult fibroblasts postinjury with
possible therapeutic intervention in the near future.
Keywords: cardiac fibrosis, postinjury, isoproterenol
4c. The Study of Arsenic-Induced Cardiotoxicity upon
Multiple Adult Cardiac Cell Types Cardiac Lineages and
Identification of Affected Downstream Regulators in Adult
Murine Heart
Sankha Banerjee, Santanu Chakraborty
Heart Development and Disease Laboratory, Department of Life Sciences,
Presidency University, Kolkata, West Bengal, India
E-mail: sankha.rs@presiuniv.ac.in
Chronic arsenic exposure associated with heart failure leads to
an increase in mortality worldwide centralizing cardiovascular
diseases. However, the detailed molecular insight toward
arsenic-mediated cardiotoxicity in adult heart homeostasis and
function is largely unknown. Therefore, our current study is
solely focused on determining the effects of arsenate upon adult
cardiac cell types, including cardiomyocytes and fibroblasts
originating from the epicardial cells through epithelial-to-
mesenchymal transition (EMT) via epicardial-derived cells in
utero. While analyzing the lineage-specific marker expression
levels, we have observed a significant increase in the
expression of activated fibroblasts in the arsenic-exposed hearts
compared to controls. Moreover, the Wheat germ agglutinin
staining, commonly used to label the glycoproteins for plasma
membrane, has shown us an increase in the cell surface area
of arsenate-exposed samples compared to control ones,
indicating hypertrophic response. Studies have shown that Yap
molecule of the Hippo-Yap signaling pathway is associated
with cellular hypertrophy as well as proliferation, leading to
proper organ size development in embryonic condition. Hence,
our hypothesis, for now, is whether Yap after getting activated
upon arsenate exposure is activating the EMT mechanism in
the adult heart to generate the activated fibroblasts from the
arsenic-exposed epicardial cells. Preliminary data have been
obtained to support EMT mechanism in adult heart by checking
the expression level of EMT-specific marker Twist1. Overall,
we try to explore the arsenate-dependent–affected signaling
pathway and its manipulation in the adult heart to reduce the
burden of cardiac pathological hypertrophy and fibrosis in vivo
with future therapeutic implications.
Keywords: cardiotoxicity, fibroblasts, expression
4d. A Critical Role of FOXM1 in Pathophysiology of
Diabetic Cardiomyopathy
Arunima Mondal, Santanu Chakraborty1, Arunima Sengupta
Department of Life Science and Biotechnology, Jadavpur University,
1
Department of Life Sciences, Presidency University, West Bengal, Kolkata,
India
E-mail: arunimasengupta2013@gmail.com
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Letter to the Editor
Cardiac diseases are one of the most common complications
with higher susceptibility in diabetic patients. Hypertrophy
of cardiomyocyte and fibrosis of heart muscle often lead
to structural and functional abnormalities, leading to risks
of heart failure. The study shown that up-regulation of
developmental regulatory molecule FOXM1 plays a important
role in pathogenesis of myocardium. As the underlying
mechanism, we have further observed that improper glucose
metabolism activates YAP1, a key organ size regulatory
molecule that further acts to activate AKT-GSK3 signaling. A
suppression of GSK3-mediated FOXM1 inactivation results
in imbalanced expression and accumulation of FOXM1 in
the cardiomyocyte. In our study, under high glucose stress,
YAP1 and FOXM1 have been found to overexpress, leading
to hypertrophic enlargement and myofibroblast differentiation.
Further, YAP1 manipulation has been resulted in a reduced
expression of FOXM1, pointing to a possible interaction
of YAP1 and FOXM1 in the cardiomyocyte. Modulation of
both these molecules also decreases the overexpression of
hypertrophic and fibrotic markers of high glucose-stimulated
cardiomyocytes. In the control cells, FOXM1 overexpression
alone has also been observed to have a profound effect on
the induction of hypertrophy of H9c2 and fibrosis, indicating
that an upregulated FOXM1 expression in the adult cardiac
myocyte cells may be a potential marker of cardiomyocyte
pathogenesis. Further observation regarding cardiac FOXM1
level may prove to be an indication of cardiac damage, as well
as therapeutic option in diabetic individuals.
Keywords: FOXM1, AKT-GSK3 signaling, myofibroblast
4e. Polyphenol-Enriched Bioactive Fraction of
Clerodendrum glandulosum Effectively Ameliorates
Oxidative Stress and Atherosclerosis, in vitro
Puspanjali Khound, Rajlakshmi Devi
Division of Life Sciences, Institute of Advanced Study in Science and
Technology, Gauhati, Assam, India
E-mail: pkhound4@gmail.com
Excess free fatty acids (FFAs) and glucose are responsible
for causing oxidative stress in patients with cardiovascular
diseases. Reactive oxygen species (ROS) oxidize and
damage DNA, proteins, and lipids, resulting in the activation
of several stress-signaling pathways that cause endothelial
injury and dysfunction, which results in the development of
atherosclerosis and cardiovascular diseases. Reduction in ROS
production and enhancement of antioxidant availability are
considered important strategies for decreasing cardiovascular
complications by utilization of herbal remedies. Clerodendrum
glandulosum is endemic to Northeast India and used in
traditional medicinal practices as a hypotensive agent. The
polyphenol-enriched bioactivity-guided fraction (PECGF)
was screened for different antioxidant and enzyme-based
assays. FFA (palmitic acid, 0.25 μM)-induced oxidative and
mitochondrial stress was effectively ameliorated by PECGF in
HepG2 cells. Pretreatment with PECGF effectively ameliorated
high levels of proinflammatory cytokines in lipopolysaccharide
Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
LPS-induced inflammation human monocytic cell line THP-1
cells. It was observed that pretreatment with PECGF exhibited
significant antiadhesion activity in high glucose-induced
atherosclerosis in vitro, in endothelial Human Umbilical
Vascular Endothelial Cell (HUVEC) and monocyte (THP-1)
cells. Therefore, these results indicate that PECGF can be
effective in the amelioration of atherosclerosis and related
cardiovascular complications.
Keywords: Atherosclerosis, cardiovascular, Clerodendrum
glandulosum, free fatty acid, reactive oxygen species
4f. Isoproterenol-Mediated Oxidative Injury Results in the
Generation of Early Cardiomyocyte Progenitor Cells in the
Adult Heart In vivo
Madhurima Ghosh, Santanu Chakraborty
Heart Development and Disease Laboratory, Department of Life Sciences,
Presidency University, Kolkata, West Bengal, India
E-mail: madhurima.rs@presiuniv.ac.in
Adult heart failure is a major public health issue, and its
prevalence is increasing in recent postpandemic times at
an alarming rate. The pathophysiological effect of oxygen
depletion during heart failure leads to the massive loss of
cardiomyocytes, which are ultimately replaced by permanent
scar tissue. Unlike zebrafish or neonatal rodent hearts with
limited cardiac regenerative capability, adult mammalian
hearts with terminally differentiated cardiomyocytes cannot
repair or regenerate damaged cardiac muscles postinjury. Here,
in this study, we have used isoproterenol for cardiac injury
induction in adult male rat hearts via generation of oxidative
stress in vivo. Adult cardiac hypertrophy and fibrosis deposition
demonstrated successful injury induction in isoproterenol-
injected animals. To our surprise, an increased number of
Wt1 and Nkx2.5-positive cells are detected in the injured
heart, indicative of epicardial activation and generation of
early cardiomyocyte lineage cells, respectively, compared
to untreated adult hearts. Interestingly, in the injured adult
hearts, the expression of epithelial-to-mesenchymal transition
markers such as Twist1 and Snail1 was also seen to be
upregulated. Furthermore, using an in vitro avian epicardial
cell culture system, the inhibition of Bmp2 signaling represses
the generation of early cardiomyocyte lineage differentiation.
Overall, knowledge of possible molecular pathway(s)
responsible for early cardiomyocyte lineage differentiation
in the injured adult heart will open up new avenues toward
cardiac repair and regenerative therapeutics.
Keywords: zebrafish, epicardial activation, epicardial activation
4g. Role of Vitronectin in Atheroinflammation
Devasmita Chakravarty1, Aleepta Guha Ray1, Vivek Chander1, Ulaganathan
Mabalirajan1, Prakash Chandra Mondal2, Khawer N. Siddiqui3, Bishnu Prasad
Sinha4, Aditya Konar5, Arun Bandyopadhyay1,4,5
Departments of 1Cell Biology and Physiology, 4Cancer Biology and Inflammatory
Disorder and 5Laboratory Animal Facility, CSIR-Indian Institute of Chemical
Biology, 2Department of Cardiology, Apollo Hospitals, 3Cardiac Research
Division, Ruby General Hospital, Kolkata, West Bengal, India
E-mail: arunb@iicb.res.in
125
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Letter to the Editor
Cellular spreading and interplay of vascular smooth muscle
cells (VSMCs), inflammatory cells, and cell adhesion
molecules (CAMs) are essential in regard to atherosclerotic
progression and cardiovascular complications. A major
cell attachment glycoprotein, whose role in atherosclerotic
pathogenesis remains elusive, is vitronectin (VTN). We
attempted to examine the pathological role of VTN in
maintaining architecture of arteries and progression of plaque.
We found that VTN levels are modulated by cholesterol levels
in vitro and in vivo by influencing its promoter. Downregulation
of VTN in vivo accelerates inflammation in atheroma along
with upregulation of proinflammatory cytokines in the plasma.
In addition, the expression of matrix metalloproteases was
increased in the plaque, in VTN-deficient conditions posing
a challenge to plaque integrity. Human subjects with acute
coronary syndrome or having risk factors of atherosclerosis
were found to have lower levels of VTN compared to healthy
controls, suggesting a clinical significance of plasma VTN
in the pathophysiology of coronary artery disease. We
establish that VTN plays a pivotal role in cholesterol-driven
atherosclerosis and aortic inflammation and might be a useful
indicator for atherosclerotic plaque burden and stability.
Keywords: pathophysiology, glycoprotein, atherosclerotic
4h. Understanding the Role of PPARα Signaling in
Oxido–Reductase Pathways in Dyslipidemic Condition
Trina Roy, Aleepta Guha Ray, Aditya Konar, Arun Bandyopadhyay
Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical
Biology, Kolkata, West Bengal, India
E-mail: trinaroy15@rediffmail.com
PPARα, a member of the peroxisome proliferator-activated
receptor family, is a ligand-activated transcription factor
predominantly expressed in tissues (liver, heart, and adipose
tissue) involved in monitoring systemic nutrient homeostasis.
Abnormalities in PPARα expression often trigger hepatic steatosis,
liver cancer, and increased risk of cardiovascular disorder, mainly
because of its uncompromised role in regulating the expression of
more than a few genes critical in lipid and lipoprotein metabolism.
PPARα ligands, “Fibrates” are frequently used in treating
dyslipidemia for their ability to lower circulating triglyceride
and elevate plasma high-density lipoprotein cholesterol. Because
PPARs are intriguing therapeutic targets for metabolic syndromes
and cardiovascular disorders, we have undertaken a multiomic
study approach to understand how cholesterol is affecting the
major pathways in dyslipidemic PPARα-deficient mice.
Keywords: ligand-activated, triglyceride, cholesterol
4i. Circulating Cell-Free DNA Acts as a Trigger toward
Extracellular Matrix Remodeling
Abhi Dutta, Moumita Das, Ankita Ghosh, Santanu Rana
Raja Peary Mohan College Integrated Biological Research Facility, Raja Peary
Mohan College, Hooghly, West Bengal, India
E-mail: abhi.dutt2018@gmail.com
Pathological cardiovascular conditions are developed due to an
increased workload and are largely associated with alterations
126 Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
in gene expression within cardiac-resident cell types. To strive,
the myocardium adapts to increased workload by structural
and functional remodeling of myocardium – known as
hypertrophy. Isoproterenol, a catecholamine, induces cardiac
hypertrophy by mimicking the sustained adrenergic stimulation
and pathogenesis of maladaptive cardiac hypertrophy.
Hypertrophic response further aggravates as an inflammatory
response, leading to a reparative phase, and a permanent
scar formation due to increased collagen accumulation in
the myocardium, leading to extracellular matrix (ECM)
remodeling along with myocyte necrosis or apoptosis.
Experimental data from our studies demonstrate an elevation
of circulating cell-free DNA (cfDNA) in the bloodstream in
induced hypertrophied mice groups compared to controls.
cfDNA are well-known Damage-associated molecular patterns
and are able to upregulate hypertrophic gene expression in
myocytes, independently. Isolated cfDNA on being treated
to H9C2 myocytes showed upregulation of atrial natriuretic
factor and beta-myosin heavy chain gene expression.
Interestingly, the cGAS-STING pathway was stimulated
during hypertrophy leading to upregulated expression of type
1 IFN and stimulated genes and NF-κB regulated downstream
inflammatory genes. Further, fibroblasts when supplemented
with media from cfDNA-induced hypertrophied H9C2 culture,
in vitro, showed an upregulation in collagen 1 and collagen
3 gene expression, associated with ECM remodeling, thereby
projecting a significant role of cfDNA toward ECM remodeling
and collagen deposition, leading to myocardial scar formation.
Keywords: hypertrophied, catecholamine, Isoproterenol
4j. Biomarkers and Drug Discovery in Cardiometabolic
Diseases
Puja Kundu
Dinabandhu Andrews College, Calcutta University, Kolkata, West Bengal, India
E-mail: kundupuja43@gmail.com
For effective drug discovery, several specific biomarkers
need to be selected. Free fatty acid (FFA) receptor 4 (FFR4),
long noncoding RNAs (lncRNAs) such as Apolipoprotein
A1 (APOA1)-AS, human lncRNA metabolic regulator
1 (hlMR1), and AK098656 are acting as biomarkers and
targets for drug delivery in several cardiometabolic diseases.
FFA causes diabetes mellitus-2 and obesity. However, it is
unable to exert its effect while bound with the FFR. FFR4
(also called G-protein coupled receptor-120) is present in
endothelial cells, adipocytes, and macrophages and enhances
the homeostatic regulations (insulin sensitivity, inflammation,
and adipogenesis) by interacting with FFA. Defective FFR4
can lead to obesity and insulin resistance. FFR4 also has a
great role in atherosclerosis. Activated FFR4 can increase
the efflux of cholesterol from macrophages and decrease the
damaged size. lncRNAs have immense roles in regulating
cardiometabolic diseases. APOA1, a key component of
high-density lipoprotein, is negatively regulated by lncRNAs
APOA1-AS epigenetically. Application of short-antisense-
oligonucleotides against APOA1-AS amplifies the expression
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Letter to the Editor
of APOA1 and also helps in the transportation of reverse
cholesterol. lncRNA hlMR1 is present in liver tissue and
participates in lipid metabolism. Activated hlMR1 can enhance
cholesterol biosynthesis whereas knockdown of it can reduce
40% or more low-density lipoprotein. Hypertensive patients
have high AK098656 lncRNA in their plasma. It regulates
the proliferation of human vascular smooth muscle cells by
binding with myosin heavy chain-11 (contractile proteins)
and fibronectin-1 (ECM proteins), causing their degradation
by 26S proteasome, and leading to hypertension. The use
of these biomarkers can help in effective drug discovery in
cardiometabolic diseases.
Keywords: proteasome, proliferation, cardiometabolic diseases
4k. Pregestational Diabetes Alters Metabolic Flexibility in
Neonatal Heart: Impact on Amino Acid and Fat Metabolism
Uppulapu Shravan Kumar, Vikas Tiwari, Md Jahangir Alam, Parul Kamboj1,
Yashwant Kumar, Sanjay K Banerjee
Department of Biotechnology, National Institute of Pharmaceutical Education
and Research, Guwahati, Assam, 1Non-Communicable Disease Group,
Translational Health Science and Technology Institute, Faridabad, Haryana, India
E-mail: shravanuppulapu@gmail.com
Background: Maternal health plays a pivotal role in
determining and predicting the health of offspring later in life.
Pregestational diabetes mellitus (PGDM) remains a major
risk for wide-ranging birth defects, such as congenital heart
defects. Chronic pathological condition such as hyperglycemia
compromises metabolic flexibility, resulting in modulation of
myocardial energetics and contractile function. However, the
metabolic reprogramming during the early development of
the heart in PGDM is largely undefined. Methods: To assess
the causal relationship, we conducted untargeted metabolic
profiling using Orbitrap fusion mass spectrometry coupled
with Ultra-performance liquid chromatography (UPLC). We
draw out the metabolic pathways involved in the perturbation
of myocardial energetics and contractile function of 7-day-old
rat hearts from neonates of PGDM mothers. We homogenized
50 mg of heart tissue collected from control and diabetic
mother-born pups in 100% methanol following standard
protocol. Systolic and diastolic functions of the pups were
assessed from M-mode ultrasound echocardiography. Results:
With the help of metabolomics, we identified a total of 322
metabolites in heart samples, of which 32 were significantly
changed. The key downregulated metabolites are kynurenic
acid, cADP-ribose, and GMP. The key upregulated metabolites
are methionine, oxoproline, asparagine, riboflavin, 4-pyridoxic
acid, and taurine. The significantly enriched pathways are
“aromatic amino acid (AAA) and branched-chain amino acid
(BCAA) biosynthesis,” biosynthesis of unsaturated fatty acids,
pyrimidine metabolism, and Vitamin B5 and B6 metabolism.
The echocardiography of the pups showed a decrease in stroke
volume, cardiac output, left ventricular mass, left ventricular
anterior wall, and left ventricular posterior wall. Conclusion:
In the present study, PGDM hearts exhibited compromised
contractility and energetics compared to control, accompanied
by extensive metabolic remodeling as demonstrated by
Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
metabolomics combined with echocardiography. The PGDM
heart metabolome showed significant differences in the
abundance of metabolites in pathways that may lead to reduced
heart rate (kynurenic acid), contractility (c-ADP-ribose,
taurine), abnormal heart development (methionine), altered
energy homeostasis and fat metabolism (pantothenic acid,
taurine, linolenate), myocardial dysfunction (4-oxoproline),
and diabetic cardiomyopathy (4-pyridoxic acid). Moreover,
increased abundance of the AAA, BCAA, and asparagine in the
neonates from diabetic mothers predicts risk of future insulin
resistance and cardiovascular disease in offspring [Figure 5].
Keywords: kynurenic acid, methionine, pantothenic acid, taurine,
linolenate
4l. Modulating Nrf2/HO-1 and TGF-β1/Smad2/3 Signaling
Cascade Ameliorates TAC-induced Cardiac Remodeling
in Mice
Abu Mohammad Syed, Sourav Kundu, Bidya Dhar Sahu
Department of Pharmacology and Toxicology, National Institute of
Pharmaceutical Education and Research, Guwahati, Assam, India
E-mail: abumohammad.syed@gmail.com
Cardiac hypertrophy is one of the significant contributors to
heart failure. Pathological cardiac hypertrophy is characterized
by excessive accumulation of extracellular matrix (ECM)
proteins and enhanced expression of hypertrophic genes, ROS
and oxidative stress, and apoptosis. Studies demonstrated that
the Nrf2 transcription factor plays a crucial role in oxidative
damage and cardiac remodeling. Daphnetin is a coumarin
isolated from the Daphne genus. It has a broader range of
pharmacological activities. In this study, daphnetin reversed
the increased cell surface area, ROS production, fibrosis, and
apoptosis protein expression stimulated by angiotensin-II in
H9c2 rat cardiomyoblasts. We found that Si-Nrf2 transfection
eliminated the protective effect of daphnetin in H9c2 cells.
However, the treatment of daphnetin increased the protein
expression of Nrf2, NQO1, and HO-1. Besides, daphnetin oral
administration normalized the cardiac functional parameters
against TAC-induced cardiac hypertrophy in mice. Furthermore,
daphnetin significantly enhanced the nuclear translocation of
Nrf2, activated many antioxidants signaling, and inhibited
oxidative damage. In addition, daphnetin downregulated the
hypertrophic mRNA markers such as α-SA, ANP, BNP, and
β-MHC. The TGFβ1/Smad2/3 fibrosis signaling axis and
ECM proteins such as fibronectin, α-SMA, and collagen were
downregulated in daphnetin-treated mice. Our study suggested
that the daphnetin treatment group significantly downregulated
TUNEL-positive nuclei, Bax/Bcl2, and cleaved caspase-3
protein expression compared to TAC group mice. Combined
results propose that daphnetin ameliorates cardiac remodeling
via modulating Nrf2/HO-1 axis, TGFβ1/Smad2/3, and apoptosis
signaling cascade [Figure 6].
Keywords: fibrosis, daphnetin, pharmacological
4m. Dopamine Beta Hydroxylase: An Optimal Target to
Counter-Hypertension
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Letter to the Editor
Varnita Anand, Sanjay Kumar Dey1, Manisha Saini2, Suman Kundu
Department of Biochemistry, University of Delhi, South Campus, 1Dr. B. R.
Ambedkar Center for Biomedical Research, University of Delhi, New Delhi,
India, 2Department of Chemistry and Chemical Biology, Rutgers University, New
Jersey, USA
E-mail: varnitaanand@south.du.ac.in
The sympathetic nervous system is an important system
involved in the pathophysiology of hypertension. An enhanced
sympathetic activity generally results in increased production
of norepinephrine (NE) and epinephrine (E), hormones
that have receptors on the heart and blood vessels and have
vasostimulatory effects that increase blood pressure. Just as α
and β blockers block the binding of NE and E on their receptors,
another direct approach is to inhibit the biosynthesis of these
hormones so as to counter the adverse effects caused due to
enhanced sympathetic activity. Dopamine beta-hydroxylase
(DBH) is an enzyme involved in the production of these
hormones. DBH converts dopamine to NE (which is converted
to E) within chromaffin granules of the adrenal medulla.
Inhibition of DBH decreases the production of NE and E,
resulting in a decreased stimulation of the adrenoreceptors on
the heart and blood vessels, thereby reducing cardiac output
and total peripheral resistance to reduce blood pressure. In
addition, this increases dopamine levels, which has a beneficial
effect, as it binds to dopaminergic receptors on renal tubules
and causes natriuresis and diuresis, lowering blood pressure.
We have found a promising inhibitor of DBH using computer-
aided drug designing. The identified hit was validated using
in vitro, ex vivo, and in vivo experiments. In this study, we
summarize the acute, subacute, and genotoxicity studies,
which have regarded the drug as nontoxic. We also present a
1-day pharmacokinetic study in a rat model showing changes
in its concentration with time after oral and intravenous
administration [Figure 7].
Keywords: sympathetic nervous system, Dopamine beta-
hydroxylase (DBH), genotoxicity
4n. Allyl Methyl Sulfide Attenuating Platelet Activation
in Diabetes by Inhibiting the Metabolism of Arachidonic
Acid Pathway
Malladi Navya, Ebin Johny1, Aishwarya Jala2, Roshan M. Borkar2, Ramu
Adela1, Sanjay Kumar Banerjee
Departments of Biotechnology, 1Pharmacy Practice and 2Pharmaceutical
Analysis, National Institute of Pharmaceutical Education and Research,
Guwahati, Assam, India
E-mail: sanjay@niperguwahati.in
Background: Platelet activation plays a pivotal role in the
pathophysiology of many cardiovascular diseases as well as
diabetes. Current antiplatelet drugs have demonstrated reduced
efficacy and increased adverse effects in diabetic patients. We
proposed that allyl methyl sulfide (AMS), an active metabolite
of garlic, could be a safe and alternative antiplatelet therapy
for diabetes. Therefore, the goal of this study was to determine
the therapeutic effect of AMS in reducing platelet activation
in diabetes and the molecular mechanism thereof. Materials
and Methods: The streptozotocin-induced diabetic rats were
128 Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
given AMS for 10 weeks. At 3-and 10-week postdiabetes,
platelet activation, aggregation, platelet–macrophage
interaction, and platelet endogenous ROS production were
assessed. In addition, we did Liquid chromatography–mass
spectrometry (LCMS)study with the platelets to understand
the molecular mechanism through metabolic alterations.
Results: The platelet activation was significantly reduced
after 10 weeks of AMS treatment, but there was no effect after
the first 3 weeks. Furthermore, at 3rd and 10th weeks, AMS
significantly reduced both baseline and ADP-induced platelet
aggregation. In addition, after 10 weeks of AMS treatment,
platelet–macrophage interactions and platelet endogenous
ROS concentration decreased. Moreover, a metabolomic
study revealed that AMS reduced numerous compounds
associated with arachidonic acid such as 15-HETE, 15-keto
prostaglandin A1, 13,14-dihydro-15-keto prostaglandin
F2 alpha, and also 7-hydroxy docosahexaenoic acid in the
platelets of diabetic rats. Conclusion: In the current study,
elevated platelet activation was linked to increased metabolites
of arachidonic acid pathways in diabetic rats. AMS attenuated
platelet activation, aggregation, and platelet–macrophage
interaction by lowering arachidonic acid pathway metabolites
in the platelets of diabetic rats [Figure 8].
Keywords: aggregation, allyl methyl sulfide, endogenous,
7-hydroxy docosahexaenoic acid
4o. Terbium Hydroxide Nanoparticle, an Innovative and
Alternative Medicine for the Treatment of Myocardial
Ischemia-Reperfusion Injury
Papia Basuthakur1,2, Arpita Roy1,2, Chitta Ranjan Patra1,2, Sumana
Chakravarty1,2
1
Department of Applied Biology, CSIR-Indian Institute of Chemical Technology,
Hyderabad, Telangana, 2Academy of Scientific and Innovative Research,
Ghaziabad, Uttar Pradesh, India
E-mail: pbthakur.211@csiriict.in
Myocardial ischemia-reperfusion injury (MIRI) is a major
and invincible underlying cause of heart failure. Considering
the escalating cost and mediocrities of current therapeutic
approaches, there is a dire need to conceive safer and more
versatile strategies for the treatment of MIRI. In this regard,
nanomedicine, with its vast meritorious applications in
biomedicine, may offer new breakthroughs in the treatment
of MIRI. In the light of this prospect, the present study was
initiated to explore the therapeutic potential of proangiogenic
terbium hydroxide nanorods (THNs) for the treatment of
MIRI. For our study, cellular model of MIRI was developed by
chemical (CoCl2) induction of hypoxia reperfusion injury (I/R) in
cardiomyocytes (H9C2). Our studies displayed major protective
role of THN by scavenging I/R-induced oxidative stress and
subsequent lipid peroxidation. In addition, THN shown to restore
impaired mitochondrial dynamics by preserving mitochondrial
membrane potential and also to restrict the progress of I/R-
induced mitochondrial apoptotic pathway by quenching the
activation of caspase 3 with simultaneously suppressing
the release of mitochondrial cytochrome C into cytosol.
Concomitantly, the treatment also compliments the survivability
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Letter to the Editor
of cells by restoring stress-induced DNA damage. Finally, THN
seems to enhance intracellular tolerance for calcium overload
and thereby may support normal cardiac rhythm. Overall, the
results warrant in-depth molecular investigations and more
comprehensive optimization of THN to be translated into clinical
research, for the treatment of MIRI [Figure 9].
Keywords: Apoptosis, calcium overload, cardiomyocyte, CoCl2,
ischemia-reperfusion, mitochondria dysfunction, oxidative stress,
terbium hydroxide nanorods
4p. Aloin Inhibits Cardiac Hypertrophy by Upregulating
Nuclear Factor Erythroid 2–Related Factor-2-Mediated
Antioxidant Responses and Alleviating TGF-β/Smad2/3
Signaling Axis
Sourav Kundu, Bidya Dhar Sahu
Department of Pharmacology and Toxicology, National Institute of
Pharmaceutical Education and Research, Guwahati, Assam, India
E-mail: kundusourav87@gmail.com
Cardiac hypertrophy is a serious concern of heart failure,
resulting in high mortality and morbidity. It can be detected
by excessive oxidative stress and extracellular matrix
accumulation. Aloin, an anthraquinone glycoside isolated from
Aloe species, has a wide spectrum of cardioprotective activities.
As the effect of aloin on cardiac hypertrophy and its mechanism
is less explored, hence we investigated. Cardiac hypertrophy
was successfully induced in male Sprague–Dawley rats by
subcutaneous isoproterenol (5 mg/kg) injection. Meanwhile,
the animals were administered aloin (25 and 50 mg/kg/day)
orally. Oxidative stress markers, echocardiographic parameters,
histopathological alterations, cardiac injury markers, fibrotic
markers, and their upstream signaling cascades were evaluated
to find the effect of aloin in attenuating cardiac hypertrophy. Our
results indicate that aloin treatment resulted in amelioration of
oxidative stress by activating master regulator of antioxidant
defense system nuclear factor erythroid 2–related factor-2
(Nrf2). Further evaluation showed that aloin increased the
translocation of Nrf2 along with the expression of antioxidant
genes NQO1 and heme oxygenase-1 (HO-1). Besides, aloin
also impeded oxidative stress by decreasing ROS generation
and increasing the antioxidant levels including superoxide
dismutase and reduced glutathione. In addition, aloin
significantly reduced the expression of hypertrophic markers
and oxidative stress in H9c2 cells. Moreover, aloin treatment
markedly reduced the fibrotic protein expression of collagen
I, α-smooth muscle actin, fibronectin, transforming growth
factor (TGF-β), and Smad2/3. Thus, aloin has the potential to
be a promising therapeutic agent that stimulates Nrf2 signaling
and blocks the TGF-β/Smad2/3 pathway and so prevents the
cardiac hypertrophy [Figure 10].
Keywords: aloin, erythroid 2–related factor-2 (Nrf2),
anthraquinone glycoside, fibronectin
4q. Efficacy and Cardiovascular Safety of SGLT-2
Inhibitors: A Network Meta-Analysis of Randomized
Controlled Trials
Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
Raja Chakraverty
Institute of Post Graduate Medical Education and Research, Kolkata, West
Bengal, India
E-mail: rchakraborty20@yahoo.com
Aim: This meta-analysis of randomized clinical trials
intended to evaluate the efficacy and safety of sodium-glucose
cotransporter 2 inhibitors (SGLT2is) have been released
recently including trials enrolling patients with congestive
heart failure (CHF) and chronic kidney disease. Methods:
We searched the PubMed, EMBASE, and Cochrane databases
for relevant studies published up until December 26, 2021.
The study protocol was preregistered in PROSPERO. The
effect size (mean difference or risk ratio [RR]) was reported
with its 95% confidence interval (CI). Results: A total of 14
trials with 89,930 participants were included in this network
meta-analysis. SGLT2is were associated with lower risks of
3P-MACE than placebo (RR 0.69, 95% CI 0.81, 0.94 and RR
0.78, 95% CI 0.81, 0.92, respectively). Conclusion: SGLT2i
affords better protection to Dipeptidyl Peptidase-4 (DPP-4)
Inhibitors in terms of cardiovascular and renal outcomes.
SGLT2i appears to be superior in reducing the incidence of
CHF and improving renal outcomes based on our findings.
Keywords: EMBASE, Cochrane databases, PROSPERO
4r. Identification of Prognostic Markers for Acute Heart
Failure using SWATH-MS-Based Plasma Proteomics
Praveen Singh1,2, Harshita Singh3, Anurag Raj1,2, Manoj Kushwaha1, Debasis
Dash1,2, Sandeep Seth3, Shantanu Sengupta1,2
1
Institute of Post Graduate Medical Education and Research, Kolkata, West
Bengal, India, 3Department of Cardiology, All India Institute of Medical Sciences,
New Delhi, 2Academy of Scientific and Innovative Research, Ghaziabad, Uttar
Pradesh, India
E-mail: praveen.singh@igib.in
Acute heart failure (AHF) is defined as a syndrome with rapid
onset or gradual worsening of signs and symptoms of heart
failure (HF) primarily as a result of pulmonary congestion. In
the presence of preexisting cardiomyopathy or an undiagnosed
de novo HF, conditions such as hypertension, coronary heart
disease, valvular heart disease, or other factors may precipitate
or induce AHF. It is characterized by high mortality and hospital
readmission rates. In the first 3 months after hospitalization,
the readmission rates are as high as 30% and the overall 1-year
mortality rates are up to 23% in India. Current treatment for
AHF is mostly symptomatic, based on decongestive drugs.
Poor management often leads to worsening of the condition.
To identify proteomic prognostic markers, we segregated AHF
patients in three categories (recovered, sick, and expired)
based on baseline and 3 months’ follow-up data of NT-pro
BNP, ejection fraction, NYHA functional classification, and
physical signs such as climbing a flight of stairs without
stopping. “Recovered” showed improvement with symptoms,
“sick” presented worsened symptoms on follow-up, while
“expired” could not survive till 3 months after their first hospital
admission. We recruited 30 patients in each category and
performed SWATH-MS-based label-free quantitative plasma
proteomics on baseline and follow-up samples. Identified
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Letter to the Editor
plasma proteins were analyzed using Boruta feature selection
algorithm to identify features (proteins) that can segregate
between the three categories of patients on baseline data. We
could identify 215 common proteins among all samples. The
feature selection tool provides 16 proteins which can act as
potential prognostic markers among AHF patients.
Keywords: pulmonary congestion, SWATH-MS, Boruta feature
selection algorithm
4s. Identification of Potential Lipid Species Associated
with Coronary Artery Disease
Salwa Naushin, Akash Kumar Bhaskar, Anurag Raj, Sandeep Seth, Debasis
Dash, Shantanu Sengupta
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
E-mail: salwa.igib@gmail.com
Background: Complex diseases such as coronary artery disease
(CAD) are controlled by various genetic, environmental, and
lifestyle factors. Lipidomic profiling is a newer approach for
identifying potential biomarkers. It could also help delineate
the mechanisms associated with cardiovascular diseases
(CVDs) since perturbation of lipid metabolism is prominent
in CVD and is one of the main mechanisms that cause disease
progression. In this study, lipid species that might be exploited
as possible biomarkers for CAD were identified using multiple
reaction monitoring (MRM)-based mass spectrometric
approach. Methods: The study was conducted at CSIR-IGIB in
collaboration with All India Institute of Medical Sciences, New
Delhi. We analyzed 304 samples (153 control and 151 CAD)
using our recently developed MRM-based lipidomic approach
where more than 1000 lipid species representing different types
of lipid classes can be identified. MultiQuant 3.0.2 software
is sufficient was used for peak review and data processing.
Results: This approach led to the identification of several
lipid species that were significantly differentially expressed
in CAD samples (adjusted by BH and confirmed/tentative
selection using Boruta random forest). We found ceramides
species, CER.24.1, CER.18.0 were elevated in CAD and
CER.24.0 were down compared to control. Plasma ceramides
have been shown to be a promising marker in the identification
of patients at risk of adverse cardiovascular events. We also
show that triglycerides containing long-chain fatty acids
and not short- and medium-chain fatty acids are associated
with CAD risk in the Indian population. Conclusions: Our
study identified a range of potential lipid biomarkers for the
differentiation of CAD. Lipid biomarkers along with clinical
predictors might be useful candidates in differentiating CAD
from healthy individuals.
Keywords: coronary artery disease, cardiovascular diseases
(CVDs), perturbation, disease progression
4t. Identification of Potential Diagnostic Markers for
Coronary Artery Disease
Salwa Naushin, Praveen Singh, Rajat Ujjainiya, Anurag Raj, Sandeep Seth,
Debasis Dash, Shantanu Sengupta
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
E-mail: rajatujjainia@gmail.com
130 Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
Background: Complex diseases such as coronary artery
disease (CAD) are multifactorial in nature. Identification of
precise markers indicative of its occurrence and progression
is important for improving disease diagnosis. Proteomic
profiling is a robust approach for exploring new biomarkers.
In this study, we utilized global proteomic approach for
the identification of proteins that can act as the potential
biomarkers for CAD. Methods: For this study, we employed
data independent approach-based SWATH-MS for the
identification of differentially expressed proteins between
control and CAD in 120 samples (60 control and 60 CAD).
Results: We are able to identify a total of 368 proteins,
of which 15 were found to be significantly differentially
expressed between control and CAD samples. Using a
random forest-based feature selection algorithm (BORUTA),
we identified a list of five proteins that could significantly
differentiate CAD from control with 77.8% confidence.
Validation of differentially expressed proteins will be
done in large sample size using targeted peptide detection
approach. Conclusions: Identification of proteins that can
significantly differentiate CAD from controls might improve
disease diagnosis and prognosis. This might further help in
understanding the disease mechanism.
Keywords: Potential Diagnostic Markers, algorithm, SWATH-MS
4u. Effect of Vitamin D Supplementation in Cardiovascular
Disease Prevention in Type 2 Diabetes Patients: Focusing
on Platelet-Mediated Inflammation
Ebin Johny, Amir Ali, Aishwarya Jala1, Bishamber Nath, Indra Kuladhipati2,
Rupam Das2, Roshan M. Borkar1, Ramu Adela
Departments of Pharmacy Practice and 1Pharmaceutical Analysis, National
Institute of Pharmaceutical Education and Research, 2Department of Cardiology,
Down Town Hospital, Guwahati, Assam, India
E-mail: amirklg1990@gmail.com
Introduction: Diabetic patients exhibit a two–four-fold higher
risk of cardiovascular disease compared to nondiabetic patients.
In type 2 diabetes mellitus (T2DM) and coronary artery
patients, increased platelet activation was observed and initiated
platelet-mediated inflammation. Moreover, severe Vitamin D
insufficiency was observed in T2DM and T2DM with coronary
artery disease patients. From previous reports, it is known
that Vitamin D plays a vital role in platelet hyperactivity and
various immune function regulations, but the effect of Vitamin
D on platelet-induced inflammation is not well studied. Hence,
we hypothesized that Vitamin D supplements might suppress
platelet-mediated inflammation and reduce the cardiovascular
disease risk in T2DM patients. Methods: We conducted a
randomized, double-blind, placebo-controlled trial in which a
dose of 60,000 IU/week of Vitamin D3 (cholecalciferol) was
given as a management dose for the first 3 months followed
by a maintenance dose of 60,000 IU/month for the next 3
months. Serum Vitamin D metabolite levels, platelet activation,
platelet-immune cell aggregate formation, and immunome
profiling were assessed at baseline and 6 months of the trial.
Results: This study has shown improvement in circulatory
Vitamin D levels in T2DM patients. Our study highlights that
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Letter to the Editor
Vitamin D supplementation downregulated platelet activation
and platelet-immune cell aggregation (P < 0.05). Moreover, it
also downregulated the serum TNF-α, IL-18, IFN-γ, CCL-2,
CCL-5, CCL-11, CXCL-10, and CXCL-12 levels compared
to the baseline levels (P < 0.05). However, Vitamin D3
supplementation does not improve the glycemic parameters.
Conclusion: The outcomes of this study suggest that supportive
therapy with Vitamin D may help decrease or minimize the risk
of cardiovascular disease development in T2DM patients by
attenuating platelet-mediated inflammation [Figure 11].
Keywords: Inflammation, platelet, Vitamin D, type 2 diabetes
4v. Acute Heart Failure Registry-II: Predictors of Acute
Outcome: A Preliminary Report
Shivani Vashista, Kavita Kumari, Deepika Jindal, Santoshi Sahani, Sandeep
Seth, Anurag Rathore1, Shantanu Sengupta2, Chandra Bhan Meena3, Deeraj
Gandotra4
Department of Cardiology AIIMS, 1Department of Chemical Engineering, IIT,
2
CSIR-Institute of Genomics and Integrative Biology, New Delhi, 3Department of
Cardiology, SMS Medical College Jaipur, Rajasthan, 4Department of Cardiology,
BLK Hospital, Delhi, India
E-mail: aiimscardiology@gmail.com
Objective: With increasing numbers of heart failure patients,
there was a serious need for studying the predictors of adverse
outcome in Indian patients with heart failure. We herein report
the in-hospital and 6-month outcomes of Indian patients
admitted with heart failure. Methods: We enrolled patients
with heart failure with systolic dysfunction in the acute failure
registry and followed them up for 6 months. We analyzed the
data on events (death, hospitalization, and any surgery during
the study) in 158 patients over 6 months. Results: A total of
158 patients were enrolled with a mean age of 0.70 ± 14.32
years, with females:male 47:111 and median age 43 years,
and the majority were male (77%). The mean left ventricular
ejection fraction was 29.2% ± 11.9%. In-hospital mortality was
20.8%. 6-month postdischarge major adverse events occurred
(mortality, re-hospitalization) combined rates were 15%. This
group had higher eGFR and liver function and higher values of
inflammatory biomarkers such as Nt proBNP. Detailed results
will be discussed. Conclusions: Indian patients with heart
failure have higher morbidity and mortality as compared to the
West. The patients who have adverse events have higher levels
of BNP and impaired renal and liver function at presentation.
These can act as markers of future adverse events.
Keywords: predictors, eGFR and liver function, morbidity and
mortality
4w. Efficacy and Safety of an Indian System of Medicine
Lifestyle Intervention Program Including Yoga in Heart
Failure: The KRYOG Randomized Controlled Trial
Sandeep Seth, Gautam Sharma, S. K. Maulik1, Raj K. Yadav 2, Shivani
Vashista, Archana Saini, Karishma Landge, Pooja Bhardawaj, Rabindra
Acharya3, Hemant Bhargava 3
Departments of Cardiology and 2 Physiology, AIIMS, Delhi, 3Swami
Vivekananda Yoga Anusandhana Samsthana) University, Bengaluru, Karnataka,
2
Dr. Subir K Maulik, Emeritus Scientist ICMR, New Delhi, India
E-mail: shivanivashista@gmail.com
Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
Background: Cardiac rehabilitation (CR) is one of the
established treatment options for heart failure. CR improves
exercise capacity, quality of life, morbidity, and mortality.
Studies of Yoga in heart failure have shown improved quality
of life, decrease in heart rate and inflammatory markers.
Objectives: The study compared the clinical outcomes of
lifestyle management through an Indian System of Medicine
including Yoga in patients with heart failure. Parameters
assessed included clinical outcomes, functional capacity
(6-min walk test), and quality of life. Methods: This was an
open-label, randomized interventional study. The intervention
arm included patients with heart failure allocated to standard
therapy for heart failure with lifestyle management through
the Indian System of Medicine including Yoga. The study
period was 6 months. Results: The intervention (KRYOG
Study) led to a significant improvement in the functional
status of the patients as manifested by the 6-min walk test
and the quality of life scores as assessed by the SF36 scales,
over 6 months. This was over and above guideline-directed
medical therapy. The Yoga intervention was safe and
effective. Conclusions: Yoga lifestyle intervention provides
improvement in functional capacity in patients on guideline-
mandated heart failure medication. DST Reference No.: SR/
SATYAM/13/2016(G). AIIMS Ethics Committee: Date
(IEC-131/04.03.2016,RP-12/2016), CTRI/2018/05/013605
(Registered on May 2, 2018).
Keywords: 6-min walk test, Yoga intervention, Medicine
including Yoga
4x. Heterogeneity among Uncontrolled Type 2 Diabetes
Patients
Sujay Krishna Maity, Jit Sarkar, Avishek Paul, Partha Chakrabarti
Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical
Biology, Kolkata, West Bengal, India
E-mail: maitysujaykrishna@gmail.com
Type 2 diabetes mellitus (T2DM) is earlier thought to be a
homogenous clinical entity but has now been recognized
as a heterogeneous disease with varying manifestations
including disease progression, drug response, and the risk
of cardiometabolic complications. Identification of these
various manifestations and disease etiologies would result
in customized T2DM management and would open up
avenues for personalized medicine. Here, health records
of 339 patients with uncontrolled T2DM were followed up
for a median period of 14 months and were analyzed using
uniform manifold approximation and projection followed
by density-based spatial clustering of applications with
noise. Oral glucose tolerance test was performed to assess
insulin resistance and β-cell dysfunction. We identified three
major clusters based on clinical parameters and various
drug combinations. Among the clusters identified, the first
cluster characterized by recent-onset T2DM had moderately
preserved β-cell function. The second cluster with a longer
duration of T2DM and associated hypertension showed
the best glycemic control with dual antidiabetic therapy.
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The third cluster with the longest history of T2DM and no
history of hypertension had the worst glycemic control in
spite of the highest percentage of patients on triple therapy
(34.58%) and quadruple therapy (8.41%). Uncontrolled
T2DM comprises a heterogeneous population concerning
disease duration, presence of hypertension, and β-cell function
without significant difference in insulin resistance. Stratifying
them based on pathological features is the first step toward
personalized management in T2DM.
Keywords: β-cell dysfunction, glycemic, Stratifying
4y. COVID-19 Infection and Outcomes of Heart-Transplant
Patients in India
Deepika Jindal, Santoshi Kumari, Shivani Vashista, Kavita Kumari, Sandeep
Seth, Manoj Kumar Sahu, Sarvesh Pal Singh, Milind P. Hote
Department of Cardiology AIIMS, New Delhi, India
E-mail: aiimscardiology@gmail.com
Introduction: Heart transplant (HT) recipients are on chronic
immunosuppressants and have an increased burden of
comorbidities. Hence, there is increased susceptibility to severe
COVID-19 infection which may result in worse prognosis.
Objectives: The aim of this study was to investigate the events
in postheart-transplant patients during different waves of
COVID-19. Events evaluated included clinical presentation,
hospitalization, home isolation, and treatment changes.
Methods: A retrospective observational study was conducted
to analyze frequency of events in 30 heart-transplant recipients
in AIIMS, New Delhi. Eleven patients were COVID-19 positive
from January 2020 to May 2022 (3 different COVID-19
pandemic waves). Results: Eleven (36.6%) heart-transplant
patients got COVID-19 infection in the first, second, and third
waves. COVID-19 infection ratio during all three waves was
4:4:3. In the first wave, 4 patients were admitted electively,
observed, and discharged with no clinical symptoms. In the
second wave, 4 patients were exposed, and due to the scarcity
of beds in the hospital, the patients were home isolated and
managed. One 65-year-old male patient desaturated, was
admitted for 1 week, kept on high-flow oxygen and steroid,
and discharged with no complications. In the third wave, three
patients who got COVID-19 were kept in home isolation and
recovered with no complications. Two patients were exposed
twice with COVID-19 in different waves of pandemic and
recovered well. Mean age of the patients was 40.1 years with
female:male ratio of 3:8. Patients clinically presented with
132 Journal of the Practice of Cardiovascular Sciences ¦ Volume 8 ¦ Issue 2 ¦ May-August 2022
fever, myalgia, cough, and anosmia. Vaccination percentage
was 72.7%. Covishield:Covaxin ratio was 4:3. Conclusion:
Patients were managed by discontinuing mycophenolate doses
and increasing steroid doses, respectively. Their hemogram
and total leukocyte count were evaluated for a week and were
discharged when values were normal. Severity of infection
was mild to moderate. Mortality was none and all patients
had good prognosis.
Keywords: Heart transplant, retrospective observational study,
COVID-19 infection, Vaccination
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Arun Bandhopadhyaya, Partha Chakrabarti1, Sanjay Banerjee2,
Shivani Kumar Vashista3, Saheli Chowdhaury
Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical
Biology, Kolkata, West Bengal, 1Cell Biology and Physiology Division (IICB)
2
Department of Biotechnology, National Institute of Pharmaceutical Education
and Research, Guwahati, Assam, 3All India Institute of Medical Science, New
Delhi, India
Address for correspondence: Dr. Shivani Kumar Vashista,
All India Institute of Medical Science, New Delhi, India.
E-mail: shivanivashista@gmail.com
Submitted: 12-Jul-2022 Published: 19-Aug-2022
Accepted: 15-Jul-2022
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DOI:
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How to cite this article: Bandhopadhyaya A, Chakrabarti P, Banerjee S,
Vashista SK, Chowdhaury S. Cardiovascular Research Convergence 2022.
J Pract Cardiovasc Sci 2022;8:117-32.
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