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ARTICLE
Monoamine oxidase is a source of oxidative stress in obese
patients with chronic inflammation1
Adrian Sturza, Sorin Olariu, Mihaela Ionică, Oana M. Duicu, Adrian O. Văduva, Eugen Boia,
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Danina M. Muntean, and Călin M. Popoiu

Abstract: Obesity is an important preventable risk factor for morbidity and mortality from cardiometabolic disease. Oxidative
stress (including in visceral adipose tissue) and chronic low-grade inflammation are the major underlying pathomechanisms.
Monoamine oxidase (MAO) has recently emerged as an important source of cardiovascular oxidative stress. The present study
was conducted to evaluate the role of MAO as contributor to reactive oxygen species (ROS) production in white adipose tissue and
vessels harvested from patients undergoing elective abdominal surgery. To this aim, visceral adipose tissue and mesenteric
artery branches were isolated from obese patients with chronic inflammation and used for organ bath, ROS production,
quantitative real-time PCR, and immunohistology studies. The human visceral adipose tissue and mesenteric artery branches
contain mainly the MAO-A isoform, as shown by the quantitative real-time PCR and immunohistology experiments. A significant
upregulation of MAO-A, the impairment in vascular reactivity, and increase in ROS production were found in obese vs. non-obese
patients. Incubation of the adipose tissue samples and vascular rings with the MAO-A inhibitor (clorgyline, 30 min) improved
vascular reactivity and decreased ROS generation. In conclusion, MAO-A is the predominant isoform in human abdominal
adipose and vascular tissues, is overexpressed in the setting of inflammation, and contributes to the endothelial dysfunction.
Can. J. Physiol. Pharmacol.

Key words: monoamine oxidases, obesity, inflammation, endothelial dysfunction.

Résumé : L’obésité est un important facteur de risque de morbidité et de mortalité liées à la maladie cardiométabolique qu’il est
possible de prévenir. Le stress oxydatif (y compris dans le tissu adipeux viscéral) et l’inflammation chronique de faible intensité
en sont les principaux modes d’action sous-jacents. La monoamine-oxydase (MAO) est depuis peu reconnue comme étant une
importante source de stress oxydatif cardiovasculaire. La présente étude a été menée en vue d’évaluer la contribution de la MAO
pour la production de dérivés réactifs de l’oxygène dans du tissu adipeux blanc et des vaisseaux sanguins prélevés chez
des patients subissant une intervention chirurgicale abdominale élective. À cette fin, nous avons isolé du tissu adipeux viscéral
et des rameaux d’artère mésentérique chez des patients obèses présentant une inflammation chronique en vue de procéder à des
études (i) en bain de tissu, (ii) sur la production de dérivés réactifs de l’oxygène, (iii) de PCR quantitatif en temps réel et
(iv) d’immunohistologie. Comme l’ont montré ces deux dernières techniques, chez l’homme, le tissu adipeux viscéral et les
rameaux d’artère mésentérique contiennent principalement l’isoforme MAO-A. Nous avons observé une régulation à la hausse
de la MAO-A, une diminution de la réactivité vasculaire et une augmentation de la production de dérivés réactifs de l’oxygène
plus marquer chez les patients obèses que chez les patients non obèses. L’incubation des échantillons de tissu adipeux et des
anneaux vasculaires avec de la clorgyline (un inhibiteur de la MAO-A) pendant 30 minutes a permis d’améliorer la réactivité
vasculaire et de faire diminuer la production de dérivés réactifs de l’oxygène. En conclusion, la MAO-A est l’isoforme prédomi-
nante dans les tissus adipeux et vasculaire abdominaux humains, est surexprimée en contexte d’inflammation et participe au
dysfonctionnement endothélial. [Traduit par la Rédaction]

Mots-clés : monoamine-oxydases, obésité, inflammation, dysfonctionnement endothelial.

Introduction adoption of the sedentary and high-caloric-intake lifestyles, par-

Obesity is the most important modifiable risk factor for mor- ticularly in developing or low-income countries, the prevalence of
bidity and mortality due to life-threatening cardiovascular dis- overweight and obesity continues to rise, including among chil-
eases, type 2 diabetes, and certain cancers. With the increased dren (Fernandez-Sanchez et al. 2011; Hruby and Hu 2015). The

Received 15 January 2019. Accepted 23 April 2019.

A. Sturza,* O.M. Duicu, and D.M. Muntean. Department of Functional Sciences – Pathophysiology, University of Medicine and Pharmacy of
Timișoara, Timișoara, Romania; Center for Translational Research and Systems Medicine, University of Medicine and Pharmacy of Timișoara,
Timișoara, Romania.
S. Olariu.* Department of Surgery II – 1st Clinic of Surgery, University of Medicine and Pharmacy of Timișoara, Timișoara, Romania.
M. Ionică. Department of Functional Sciences – Pathophysiology, University of Medicine and Pharmacy of Timișoara, Timișoara, Romania.
A.O. Văduva. Department of Microscopic Morphology – Morphopathology, University of Medicine and Pharmacy of Timișoara, Timișoara, Romania.
E. Boia and C.M. Popoiu. Department of Pediatry – Pediatric Surgery, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Timișoara,
Romania.
Corresponding author: Danina Muntean (email: daninamuntean@umft.ro).
*These authors contributed equally to this work.
1This paper is part of a Special Issue of selected papers from the 5th European Section Meeting of the International Academy of Cardiovascular Sciences held

in Smolenice, Slovakia, on 23–26 May 2018.

Copyright remains with the author(s) or their institution(s). Permission for reuse (free in most cases) can be obtained from RightsLink.

Can. J. Physiol. Pharmacol. 00: 1–6 (0000) dx.doi.org/10.1139/cjpp-2019-0028 Published at www.nrcresearchpress.com/cjpp on 3 May 2019.
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2 Can. J. Physiol. Pharmacol. Vol. 00, 0000
expanded adipose tissue is responsible for the inflammatory en-
vironment (Pereira and Alvarez-Leite 2014) and high generation of
reactive oxygen species (ROS), the 2 pathomechanisms of obesity-
related complications (McMurray et al. 2016). Indeed, the low-
grade chronic inflammation and oxidative stress at the level of
adipose tissue (mainly visceral) are the major contributors to the
occurrence of type 2 diabetes and accelerated atherosclerosis in
the setting of obesity that currently affects 1/3 of people world-
wide, hence the term “globesity” (Afshin et al. 2017).
Several intracellular sites have been identified as being respon-
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sible for ROS production, with the mitochondrial respiratory
chain at the inner mitochondrial membrane (Muntean et al. 2016;
Murphy 2009) and NADPH oxidases being particularly involved
(Brandes and Schroder 2008).
In the past 2 decades, monoamine oxidases (MAOs) with 2
isoforms, A and B, at the outer mitochondrial membrane have
emerged as important sources responsible for oxidative stress
in the cardiovascular system in pathological conditions (Di Lisa
et al. 2009; Kaludercic et al. 2014b). These flavin-dehydrogenases
catalyze the oxidative deamination of neurotransmitters and bio-
genic amines (serotonin, dopamine, and norepinephrine) with
the constant generation of hydrogen peroxide, aldehydes, and am-
monia as deleterious by-products (Di Lisa et al. 2009; Kaludercic et al.
2014a).
MAO-A is classically considered the major isoform in the cardio-
vascular system that increases with ageing and is responsible for
the related cardiac oxidative damage (Kaludercic et al. 2011) and
also mediates the maladaptive evolution of ventricular hypertro-
Can. J. Physiol. Pharmacol.
phy towards heart failure (Kaludercic et al. 2014a), the endothelial
dysfunction in the setting of hypertension (Sturza et al. 2013a,
2013b), inflammation (Sturza et al. 2013a), chronic kidney disease
(Utu et al. 2017), and diabetes (Duicu et al. 2016; Lighezan et al.
2016; Sturza et al. 2015b).
Scarce literature is available on MAOs contribution to oxidative
stress in the adipose tissue. There are a couple of studies that
reported an increased MAO activity in the white adipose tissue in
obese mice (Tong et al. 1979) and dogs (Wanecq et al. 2006). As for
humans, a pioneering study from Pizzinat et al. identified high
MAO activities in abdominal and mammary human adipocytes
and reported their role in the clearance of plasma norepinephrine
(Pizzinat et al. 1999). More recently, MAO expression was reported
to be increased during adipogenesis in human adipocytes (Bour
et al. 2007).
However, no data are available concerning the role of these
enzymes in the visceral adipose tissue in obesity associated with
systemic inflammation. Thus, the aim of the present study was to
investigate the MAO contribution to oxidative stress in adipose
tissue and vascular samples harvested from patients with obesity
and chronic inflammation.
Materials and methods
Samples of omental adipose tissue and mesenteric arteries were
obtained from consecutive patients undergoing abdominal sur-
gery. Patients were randomized into 2 groups: (1) obese patients
with an inflammatory status (n = 10; 4 women, 6 men), and
(2) non-obese patients without inflammation (n = 10; 5 women, 5
men).
The University Committee for Research Ethics approved the
study protocol (No. 11/31.03.2017) and informed consent was ob-
tained from all patients prior to surgery, according to the World
Medical Association Declaration of Helsinki.
Immunohistochemistry studies
Tissue expression of the MAO was quantified in frozen sections
of human intra-abdominal adipose tissue and branches of mesen-
teric arteries using the MAO-A (ab126751, 1:50; Abcam) primary
antibody and Alexa Fluor labeled secondary goat anti-rabbit anti-
body (A32731, 1:200; Invitrogen), respectively, as previously de-
scribed (Sturza et al. 2015a, 2015b, 2018). Nuclear staining was
obtained with DAPI (SC3598, Santa Cruz Biotechnology). The
slides were examined using an Olympus Fluoview FV1000 confo-
cal microscope (DAPI ex/em 405/461 nm, Alexa Fluor ex/em 543/
612 nm). Images were analyzed with Icy, a free open-source image
analysis software, developed by the Quantitative Image Analysis
Unit at Institute Pasteur (Paris, France) (de Chaumont et al. 2012).
Oxidative stress assessment by means of ferrous iron
xylenol orange oxidation assay
Hydrogen peroxide production was assessed in samples of vis-
ceral adipose tissue and branches of mesenteric arteries in the
presence vs. absence of the MAO-A inhibitor, clorgyline (10 ␮M,
30 min incubation), using the ferrous iron xylenol orange oxida-
tion (FOX) assay (PeroxiDetect Kit; Sigma–Aldrich) as previously
described (Danila et al. 2017; Lighezan et al. 2016; Sturza et al.
2013a, 2015b, 2015c, 2018; Utu et al. 2017). The principle of the assay
is that peroxides oxidize Fe2+ to Fe3+ ions at acidic pH. The Fe3+ ion
will form a colored adduct with xylenol orange, which is spectro-
photometrically measured at 560 nm. Subsequently, the produc-
tion of H2O2 was calculated using the standard curve. The result is
expressed in nanomoles of H2O2 per hour per milligram of tissue.
Oxidative stress assessment by means of
immunofluorescence
The total amount of ROS was determined using the dihy-
droethidium (DHE) probe according to a previously described
technique (Duicu et al. 2016; Miller et al. 2008). Briefly, the sam-
ples were embedded in optimal cutting temperature compound
and snap-frozen. The frozen fragments were cut in 8 ␮m thick
cryosections and put on glass slides. After 3 washes with PBS,
5 min each, the cryosections were incubated in the dark with DHE
for 30 min at room temperature. Excess DHE was removed by
3 additional washes with PBS. The slides were mounted with
Vectashield (Vector Laboratories) and immediately analyzed using
a confocal microscope (Olympus Fluoview FV1000). Images were
obtained using laser excitation at 488 nm. Image analysis was
performed using Icy Bioimage Analysis software (de Chaumont
et al. 2012).
Real-time PCR
All tissues were homogenized using the Tissue Lyser (QIAGEN).
Total RNA was isolated (Total RNA Mini SI Isolation Spin-Kit; Ap-
plichem), measured using a Nanodrop 2000 spectrophotometer
(Thermo Scientific) and used for reverse transcription (Super-
script III RT; Invitrogen). Quantitative real-time-PCR (Biorad) was
performed in adipose tissue and vascular samples. Primers against
MAO isoforms were designed using sequence information from
the NCBI database (5=¡ 3=): human MAO-A forward, 5=-CTG ATC
GAC TTG CTA AGC TAC-3=; human MAO-A reverse, 5=-ATG CAC
TGG ATG TAA AGC TTC-3=. The housekeeping gene (EEF2, eukary-
otic elongation factor 2) and its primers were as follows (5=¡ 3=):
EEF2 forward, GAC ATC ACC AAG GGT GTG CAG; EEF2 reverse,
GCG GTC AGC ACA CTG GCA TA.
Vascular reactivity studies
The vascular samples (mesenteric artery branches) were mounted in
the myograph (DMT) chambers filled with 5 mL of Krebs solution
(37 °C) aerated with 95% O2-5% CO2 gas mixture (pH 7.4). The rings
were stretched to an optimal tension of 1 g, allowed to equilibrate
for 45 min, and further exposed to 80 mM KCl. The concentration
of phenylephrine used for preconstriction was adjusted to obtain
a preconstriction level of 80% of the contraction elicited by KCl
(80 mM). Endothelium-dependent relaxation to cumulative con-
centrations of acetylcholine and contractility to nitric oxide syn-
thase inhibitor N␻-nitro-L-arginine (L-NAME, 10 ␮M) were recorded
in the presence vs. absence of irreversible MAO-A inhibitor, clor-
gyline (10 ␮M). Nitric oxide bioavailability was estimated from the
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Sturza et al. 3

Table 1. Characteristics of the study groups. Fig. 1. Monoamine oxidase (MAO) is expressed in human adipose
tissue and vasculature and is upregulated in setting of obesity.
OB non-OB
(A) MAO expression in human intra-abdominal adipose tissue and
(BMI ≥ 30 kg/m2), (BMI < 30 kg/m2),
mesenteric artery branches in immunofluorescence: green, anti-
n = 10 (4乆, 6么) n = 10 (5乆, 5么) P
MAO-A antibody; blue, DAPI. (B) MAO-A expression (fold change) in
Age (years) 45–66 43–68 Ns visceral adipose tissue and mesenteric artery branches from obese
Blood pressure (mm Hg) 135±12/83±10 137±21/88±4 Ns (OB) and non-obese (nonOB) patients (quantitative real-time PCR)
Heart rate 98±29 100±21 Ns *p < 0.05. [Colour online.]
Cell blood count
RBC (million/mm3) 4.51±0.08 4.32±0.7 Ns
Hematocrit (%) 38.74±1.34 39.56±4.11 Ns
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Hemoglobin (g/dL) 12.66±0.5 13.05±0.21 Ns

WBC (×103/mm3) 10.7±7.3 7.2±0.5 Ns
PLT (×103/mm3) 266.8±37.2 305.3±21.8 Ns
ESR (mm/h) 39±16 12.3±4.5 <0.05
C reactive protein (mg/L) 45.33±4.7 9.21±3.6 <0.05
Urea (mg/dL) 34±3.4 29.88±5.97 Ns
Creatinine (mg/dL) 0.96±0.1 0.98±0.11 Ns
Uric acid (mg/dL) 4.7±0.3 4.91±1.81 Ns
Total cholesterol (mg/dL) 221.7±12 188.7±8.71 Ns
HDLc (mg/dL) 38±5.3 49.8±11 <0.05
LDLc (mg/dL) 157±6 142±7.34 Ns
Triglycerides (mg/dL) 140.45±21 125±23.5 Ns
Blood glucose (mg/dL) 102±1.6 99.5±8.23 Ns
Hemoglobin A1c (%) 5.2±0.3 5.3±0.14 Ns
ALAT (U/L) 32.4±6.2 28±2 Ns
ASAT (U/L) 22.6±5.56 20±3 Ns
Total serum calcium (mg/dL) 8.6±0.45 8.72±0.4 Ns
Ionized calcium (mg/dL) 4±0.34 4.89±0.5 Ns
Serum phosphate (mg/dL) 5.2±0.3 5.3±0.14 Ns
Can. J. Physiol. Pharmacol.

Note: Data are means ± SEM and significant differences are in boldface type.
OB, obese; RBC, red blood cells; WBC, white blood cells; PLT, platelets; ESR,
erythrocyte sedimentation rate; HDLc, high-density lipoprotein cholesterol;
LDLc, low-density lipoprotein cholesterol; ALAT, alanine aminotransferase;
ASAT, aspartate aminotransferase; Ns, not significant.

constrictor response (%) to the classic NO synthases inhibitor,

L-NAME (10 ␮M) in vascular rings preconstricted with phen-
ylephrine to 10% of the maximal KCl constriction.

Statistics
Data are presented as mean ± SEM and were analyzed using a
one-way ANOVA or Student’s t test when appropriate. Data anal-
ysis of the dose–effect response curves was performed using the
ANOVA F test (comparisons of bottom and top values, EC50, and
the Hill slope). Values of p < 0.05 were considered statistically
significant.
Results
Characteristics of the study groups
The characteristics of patients included in the study are pre-
sented in Table 1. As shown, a mild inflammatory status was pres-
ent in the obese group as compared with the non-obese one, as
documented by the increased values of both C reactive protein
and erythrocyte sedimentation rate, the latter being the hallmark
of a chronic inflammatory status. Also, a significant lower value of
high-density lipoprotein cholesterol was found in the obese pa-
tients.
MAO is expressed in the visceral adipose tissue and
mesenteric artery branches
Limited information is available regarding the MAO expression
in human visceral adipose tissue and mesenteric vessels. For this
reason, we evaluated the expression of MAO isoforms in adipose
tissue samples and arterial fragments isolated from patients sub-
jected to elective abdominal surgery by means of immunohistol-
ogy. The results showed that both MAO isoforms were present
with predominance of the MAO-A (Fig. 1A). MAO was diffusely
distributed in the adipose tissue, whereas in the vascular wall we
noticed an increased expression in the intima and the adventitia
(Fig. 1A).
Obesity and chronic inflammation are associated with
increased MAO-A expression in both adipose tissue and
vasculature
Increased oxidative stress in the adipose tissue and vasculature
is the hallmark of overweight and obese patients but the sources
of ROS are partially elucidated. While the classical sources still
remain NADPH oxidases and the mitochondrial respiratory chain,
we report here that MAO-A isoform contributes to the adipose
tissue and vascular oxidative stress, being upregulated in samples
isolated from obese patients with chronic inflammation, as re-
vealed by the mRNA gene expression (Fig. 1B).
MAO-A is a source of ROS in adipose tissue and vasculature
when obesity coexists with inflammation
As MAO-A was upregulated in the adipose tissue and vascular
preparations from obese patients, we further assessed the ROS
production by immunohistology and FOX assay after incubating
the samples with the MAO-A inhibitor, clorgyline (10 ␮M, 30 min).
Ex vivo incubation with clorgyline was able to reduce the signal
related to oxidative stress as revealed by DHE staining (Figs. 2A,
2B) and rate of hydrogen peroxide production measured by FOX
assay (Fig. 2C).

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4 Can. J. Physiol. Pharmacol. Vol. 00, 0000

Fig. 2. Monoamine oxidase (MAO) is a source of oxidative stress in human adipose tissue and vasculature. The effect of MAO-A inhibitor
clorgyline (Clorg, 10 ␮M) on oxidative stress in (A) adipose tissue and (B) mesenteric artery branches samples harvested from obese (OB) and
non-obese (nonOB) patients (dihydroethidium stain). (C) The effect of MAO-A inhibitor clorgyline (Clorg, 10 ␮M) on hydrogen peroxide
production in adipose tissue and mesenteric artery branches from obese (OB) and non-obese (nonOB) patients (ferrous iron xylenol orange
oxidation (FOX) assay). *p < 0.05. [Colour online.]
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Can. J. Physiol. Pharmacol.

MAO inhibition improves vascular reactivity of mesenteric Discussion

branches isolated from obese patients with inflammation
Because we noticed an upregulation of MAO-A together with an
increased amount of ROS in the vessels, we thought to determine
whether MAO inhibition is also able to modulate the reactivity of
the vascular preparations in organ bath studies. Vascular contrac-
tility in samples obtained from obese patients with inflammation
was significantly increased in response to cumulative doses of
phenylephrine, whereas the endothelium-dependent relaxation
was significantly attenuated. Incubation with the irreversible
MAO-A inhibitor restored both the contractile and relaxation re-
sponses (Figs. 3A, 3B). Also, contractility to L-NAME (10 ␮M), the
classic nitric oxide synthases inhibitor, was significantly in-
creased in samples from obese patients; this response was re-
duced after clorgyline (Fig. 3C), a finding that strongly suggests
the involvement of nitric oxide in the vascular protective effect of
MAO inhibition.
The main finding of this pilot study is that MAO-A isoform
contributes to the adipose tissue and vascular oxidative stress in
the setting of obesity and systemic inflammation. These observa-
tions are particularly important because a persistent, dysfunc-
tional low-grade inflammatory status is the hallmark not only of
obesity but also of all noncommunicable chronic diseases of the
21st century (Bennett et al. 2018). The obesity-driven changes of
the adipose tissue microenvironment are responsible for the
chronic systemic inflammation via the upregulation of the pro-
inflammatory cytokines and the downregulation of the anti-
inflammatory ones, as recently reviewed (Fuster et al. 2016).
Also, the increased oxidative stress in the setting of obesity has
been systematically investigated, in particular the role of dysfunc-
tional complexes of the electron transport chain (McMurray et al.
2016). Here, we unequivocally demonstrated that MAO is an im-

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Sturza et al.
Fig. 3. Monoamine oxidase (MAO-A) inhibition improves vascular
reactivity in human mesenteric artery branches. (A) Phenylephrine
(Phe)-induced contractions, (B) acetylcholine (Ach)-induced
endothelium-dependent relaxation, and (C) contraction to
N␻-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 ␮M),
in human mesenteric arteries branches obtained from obese (OB)
and non-obese (nonOB) patients, incubated or not with MAO-A
inhibitor, clorgyline (Clorg, 10 ␮M, 30 min). *p < 0.05 OB vs.
nonOB, #p < 0.05 OB vs. OB + Clorg.
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Can. J. Physiol. Pharmacol.
portant contributor to the oxidative stress in obese patients with
chronic inflammation. Indeed, MAO inhibition was able to signif-
icantly reduce the amount of H2O2 in the white adipose tissue and
vascular samples from obese patients. Of note, in a previous study,
we firstly noticed the presence of MAO in the perivascular adipose
tissue of coronary arteries isolated from patients with coronary ar-
tery disease (Lighezan et al. 2016) — an observation that prompted
this study. In our hands, ex vivo MAO inhibition elicited beneficial
effects in several studies performed in human vascular samples,
such as internal mammary arteries isolated from patients sub-
jected to coronary by-pass surgery (Lighezan et al. 2016) and in
collaterals of brachial artery in patients with chronic kidney dis-
ease with indication of hemodialysis (Utu et al. 2017).
Interestingly, irreversible MAO-A inhibition with clorgyline
elicited a significant reduction of oxidative stress only in adipose
tissue samples harvested from the obese group as revealed by the
DHE staining and FOX assay, respectively. However, in organ bath
experiments, clorgyline was able to reduce contractility in all the
vascular rings, regardless of the study group. This observation is
suggestive for both tissue specificity and pleiotropic effects of
MAO inhibitors (behind MAO inhibition). In an earlier study, we
investigated whether MAO inhibitors act as ROS scavengers, a
hypothesis that was not confirmed (Sturza et al. 2013a). However,
because clorgyline was able to reduce the contractility to L-NAME,
we speculate that its beneficial effect is mediated via an interac-
tion with the nitric-oxide-dependent pathway. In this respect, we
have previously observed in human umbilical vein endothelial
cells that MAO directly interfere with nitric oxide signaling path-
way and limit the accumulation of cyclic guanosine monophos-
phate (Sturza et al. 2013a).
5
The presence of MAO-A has been documented together with the
one of semicarbazide-sensitive amine oxidase in the mesenteric
perivascular adipose tissue from rats (Ayala-Lopez et al. 2017). In-
terestingly, these authors reported that individual inhibition of
either enzyme did not alter the contractility to norepineprine;
however, inhibition of both MAO and semicarbazide sensitive
amine oxidase increased the effect of norepinephrine on mesen-
teric arteries with peripheral adipose tissue. We acknowledge as
limitations of our study the fact that we did not assess the enzy-
matic activity and protein expression or putative crosstalk with
other amine oxidases. Also, the level of free fatty acids, which may
directly interfere (when increased) with the vascular reactivity via
a direct membrane effect, was not measured.
The constant interest in studying ROS sources in the cardiovas-
cular system stems from the fact that cardiovascular diseases and
their comorbidities (obesity, metabolic syndrome, and diabetes)
remain the leading causes of morbidity and mortality worldwide,
despite a huge and constantly expanding therapeutic armamen-
tarium. All of these pathologies have common pathogenesis that
include the triple association of endothelial dysfunction, “low-
grade” inflammation, and oxidative stress, all cumulatively con-
tributing to disease progression and complications. Nevertheless,
whether the increased MAO expression in the visceral adipose
tissue is a cause or a consequence of the prolonged low-grade
inflammatory status remains an open question.
MAO inhibitors have been systematically studied starting from
the mid-past century for their therapeutic efficacy in neurodegen-
erative and psychiatric illnesses (including depression) via com-
plex mechanisms that include the mitigation of the oxidative
stress (Bortolato et al. 2008; Song et al. 2013). Therefore, in line
with the recently reported association between a higher body
mass index and depression, particularly in women (Tyrrell et al.
2018), the study of the new generations of reversible MAO inhibi-
tors as potential candidates for drug repurposing in the treatment
of cardiometabolic diseases represents a feasible alternative. A
starting point could be represented by the assessment of the ef-
fects of MAO inhibition on the systemic inflammatory status in
the setting of chronic noncommunicable diseases.
Conclusions
MAOs are expressed in human visceral adipose tissue and
branches of mesenteric artery, and the MAO-A isoform is upregu-
lated in the setting of obesity associated with chronic inflamma-
tion. In vitro inhibition of MAO-A significantly reduced the
amount of oxidative stress in both adipose tissue and arteries;
in the latter, an improved vascular reactivity (reduced contrac-
tility and increased endothelium-dependent relaxation) was
also found. These data also suggest that MAO inhibitors are prom-
ising candidate compounds for drug repositioning.
Conflict of interest
The authors declare that there is no conflict of interest associ-
ated with this work.
Acknowledgements
This research was supported by the university grant PIII-C5-
PCFI-2017/2018-01.
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