Perilla oil and exercise decrease expressions of tumor necrosis fac-tor-α, plasminogen activator inhibitor-1 and highly sensitive C-reac- tive protein in patients with hyperlipidemia

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com J Tradit Chin Med 2013 April 15; 33(2): 170-175


info@journaltcm.com ISSN 0255-2922
© 2013 JTCM. All rights reserved.

CLINICAL STUDY
TOPIC

Perilla oil and exercise decrease expressions of tumor necrosis fac-


tor-α, plasminogen activator inhibitor-1 and highly sensitive C-reac-
tive protein in patients with hyperlipidemia

Minggang Wei, Peihua Xiong, Ling Zhang, Mei Fei, Aiping Chen, Fengling Li
aa
Minggang Wei, Peihua Xiong, Ling Zhang, Mei Fei, Aip- liver or kidney function, or blood routine examina-
ing Chen, Fengling Li, the First Affiliated Hospital to Sooch- tions.
ow University, Suzhou 215006, China
Correspondence to: Prof. Minggang Wei, the First Affiliat- CONCLUSION: Perilla oil treatment is safe in clinical
ed Hospital of Soochow University, Suzhou 215006, China. use, can regulate blood lipid levels and protects
weimg@sina.com
the function of endothelial cells.
Telephone: +86-13812791993
Accepted: November 14, 2012

© 2013 JTCM. All rights reserved.

Key words: Fructus perillae; Tumor necrosis fac-


Abstract tor-alpha; Plasminogen activator inhibitor 1; C-reac-
OBJECTIVE: To verify the effects of perilla oil on the tive protein; Hyperlipidemias
regulation of blood lipid levels in patients with hy-
perlipidemia.
INTRODUCTION
METHODS: Blood was taken from patients prior to Lipid-lowering therapy has been proven to give surviv-
and 8 weeks following treatment with perilla oil. al benefits to patients with hypercholesterolemia by
Different ways to test for indexes which correlate to preventing both primary and secondary cardiovascular
hyperlipidemia were performed. Some indexes, disease.1 The mechanisms of these beneficial effects can
which correlate with inflammation and injury to en- be, in part, explained by a reduction in plasma lipid
dothelial cells, were tested using enzyme linked im- levels.2-4 Non-lipid mechanisms may possibly involve re-
munosorbent assays. ducing inflammation, decreasing thrombogenicity, pla-
quing stabilization and reversing endothelial dysfunc-
RESULTS: Serum lipid levels [triglyceride (TG), total tion.5 Statins are currently the most common drugs dis-
cholesterol (TC), and low-density lipoprotein-cho- playing the best results for lowering low-density lipo-
lesterol (LDL-C)] changed significantly after 56 days protein (LDL) cholesterol.5 Statins also possess anti-in-
of treatment. Differences were noted as early as 28 flammatory properties,6,7 and have a positive effect on
reducing arterial stiffness.8,9 However, two major ad-
days after treatment began (P<0.05). Treatment
verse effects accompany statin therapy: hepatic dysfunc-
with perilla oil showed statistically significant recov-
tion and muscular toxicity.
ery levels of high-density lipoprotein-cholesterol Perilla oil is extracted from Fructus Perillae. A soft cap-
(HDL-C) after 28 and 56 days of treatment. Plasma sule of perilla oil is produced by Sanai (Fujian) Pharma-
lipids levels were significantly lower after 56 days of ceutical Co., Ltd. (production lot: 080803, 081101,
treatment (P<0.05). Perilla oil reduced blood lipid 081102). Perilla oil is a new product to be extracted
levels in patients, and the regulation of cell signal- from a Chinese herb, and does not impair dietary pro-
ing factor levels had no adverse effects on patients' cesses nor does it affect the absorption of triglycerides

JTCM | www. journaltcm. com 170 April 15, 2013 | volume 33 | Issue 2 |
Wei MG et al. / Clinical Study

or fat-soluble vitamins. Perilla oil is effective treatment underwent clinical examinations and blood tests to es-
as therapy or as an adjunctive therapy in combination tablish a baseline, and were then again subject to exami-
with statins. It is well tolerated in clinical trials with no nations and blood tests after 4 and 8 weeks of treat-
demonstrable adverse systemic events.10 The effects of ment. Perilla oil capsules were taken 4 grain/time,
perilla oil on arterial stiffness have not yet been investi- twice/day. Eight weeks was defined as a course of treat-
gated. ment.
The aim of the present study is to assess the effect of Hs-CRP levels of patients with high blood fat were
perilla oil therapy on highly sensitive C-creative pro- measured before treatment and again after 56 days of
tein (hs-CRP) and endothelial function. treatment. The levels of TC, TG, LDL-C and HDL-C
were measured to establish a baseline and again after
28 and 56 days of treatment. Acute-phase reactant tu-
MATERIALS AND METHODS mor necrosis factor-α (TNF-α) and plasminogen acti-
vator inhibitor-1 (PAI-1) were measured on the same
Patient selection days as hs-CRP.
Inclusive criteria: men or women aged 18-75 years with After a 12 h limosis, potential patients were screened
a baseline total cholesterol (TC) ≥6.22 mmol/L or tri- and underwent a phlebotomy for liver function tests in-
glyceride (TG) ≥2.26 mmol/L or high density lipopro- cluding total bilirubin, aspartate aminotransferase
tein-cholesterol (HDL-C)≤1.04 mmol/L or low-density (AST), alanine aminotransferase (ALT), alkaline phos-
lipoprotein-cholesterol (LDL-C)≥4.14 mmol/L were in- phatase, blood urea nitrogen (BUN), creatinine, glu-
volved in the study. Patients were required to stop tak- cose, complete blood count, electrocardiogram (ECG),
ing any medication for a minimum of 7 days before and a urinalysis. The EG group was only treat by with
the study commenced. exercise, MG group was only treat by perilla oil cap-
Exclusion criteria: patients were excluded if they ules, EMG group was treat by both exercise and perilla
showed clinical evidence of previous cardiovascular dis- capules.
ease (defined as a past history of myocardial infarction, Following the guidelines for protecting and treating
percutaneous transluminal coronary angioplasty or a high blood plasma for Chinese adults, patients were giv-
coronary artery bypass graft); had had a failed organ en oral and written instructions to perform 30-60 min
transplant or malignant tumor requiring treatment in of brisk walking per day at least 4 days per week, with
the last two years; showed active hepatic or renal dys- an interval of no more than 2 consecutive days.11,12 Pa-
function; showed any type of connective tissue disease, tients were also encouraged to increase their daily activ-
chronic inflammatory disease, malignancy or history of ities. The main goal for each individual was to accumu-
malignancy; showed any acute illness, leukocytosis or late more than 150 min per week of self-directed, mod-
thrombocytosis, anemia or diabetes mellitus; or were erate-intensity physical activity. Exercises intensities, in-
taking corticosteroids. The use of tobacco, which in- cluding walking, cycling and calisthenics, were individ-
creases C-reactive protein (CRP), and aspirin, which ualized. The intensity of each session gradually in-
decreases CRP, was outside the exclusion criteria as pa- creased to 50%-70% of a patient's peak oxygen con-
tients controlled their own behavior. sumption and up to 60 min duration for the first 4
Test subjects were instructed to avoid using non-steroi- weeks. After that, the exercise parameters remained
dal anti-inflammatory agents. Patients' medical regi- constant.
mens were not changed throughout the study period.
Sample collection
The study was approved by the ethics committee of the
Venous blood was drawn from patients who had an
second hospital affiliated to Tianjin University of Tradi-
empty stomach for at least 8 h before treatment, and
tional Chinese Medicine. All participants gave written
again after 28 and 56 days of clinical intervention. Sera
informed consent in accordance with the Declaration
was immediately centrifuged for 5 min at 2000 rpm to
of Helsinki.
remove cells and debris, and then stored at –80℃ for
no more than 4 months before measurement. For clini-
Study design
cal safety, urine, serum creatinine (Scr), ALT and ECG
The study used a prospective, random control design.
were tested before treatment and again after 56 days of
All patients were randomly allocated into 3 groups us-
clinical intervention.
ing the random number table method. Thirty-six pa-
tients with elevated blood lipids defined by the Nation- Enzyme-linked immunosorbent assay (ELISA)
al Preventing Program for the Chinese adult with high ELISA was used to detect TNF-α and PAI-1 in sera.
blood lipids: Adult Treatment Guideline 2007.12 Briefly, plates were blocked and incubated at room tem-
Eligible patients (n=36) gave informed consent and perature for 2 h, washed with wash buffer 4-6 times
were randomly divided into: 1) an exercise group (EG) and dried with filter paper. Biotinylated antibodies
(n=12); 2) a medicine group (MG) (n=12), which were added to samples (100 μL per hole) and incubat-
were treated with perilla oil capsules; and 3) an exercise ed for 1 h at 37℃. Washing and the addition of bioti-
and medicine group (EMG) (n=12). The patients first nylated antibodies was performed in duplicate. Reac-

JTCM | www. journaltcm. com 171 April 15, 2013 | volume 33 | Issue 2 |
Wei MG et al. / Clinical Study

tions were stopped by the addition of stop solution TG, TC, hs-CRP, PAI-1, TNF-α and cell signaling fac-
(100 uL per hole). Plates were read at a wavelength of tors in EMG show greater change than both EG and
450 nm on a microplate reader (JETLIA-962 System, MG; and a better curative effect is achieved in EMG
Beijing, China). Liver and renal functions (ALT and than in the other two groups; 4) by comparing the cu-
Scr) were tested using an automatic biochemistry ana- rative effect of regulating plasma lipids between EG,
lyzer (Olympus AU-2700, Tokyo, Japan). hs-CRP was MG and EMG after 56 days of treatment, the curative
tested using the rate dispersion turbidity method with effect of both exercise and perilla oil in EMG is better
a special protein analysis instrument (Beckman-Array than that in the other two groups; 5) perilla oil can reg-
360, Danvers, Massachusetts, USA). ulate and protect endothelial cells through regulation
of the levels of hs-CRP, PAI-1 and TNF-α; and there is
Statistical analyses no side-effects, such as hepatic dysfunction or muscu-
Statistical analyses were performed with SPSS software lar toxicity; and 6) both exercise and perilla oil regulate
(SPSS, Chicaga, IL, USA), version 15. Significance plasma lipid levels and protect endothelial cell func-
tests were 2-sided. A value of 0.05 was considered sta- tion, but integrating them together in clinical practice
tistically significant. All data are expressed as the mean would give better benefits to patients.
± SEM.
Safety indexes
We tested the levels of white blood cells (WBC), AST,
RESULTS ALT, BUN and Scr as the markers of safety indexes. All
safety index levels fluctuated around the normal range
before and after the study (Table 3).
General condition
Serum lipid levels (TG, TC and LDL-C) changed sig-
nificantly after 56 days of treatment. Differences were DISCUSSION
noted as early as 28 days after treatment began (P<
0.05) (Table 1). Treatment with perilla oil showed sta- Chronic heart diseases are often complicated by dyslip-
tistically significant recovery levels of HDL-C after 28 idemia in many patients in clinical practice. Lipid ab-
and 56 days of treatment. Plasma lipids levels were sig- normalities include increases in serum TG-associated li-
nificantly lower after 56 days of treatment (P<0.05) poproteins (intermediate density lipoproteins and very
(Table 1). There was no statistical differences in levels low density lipoproteins) and LDL, and decreases in
of hs-CRP, PAI-1, TNF-α or plasma lipid between the HDL-C. The leading cause of death in patients with
EG, EM and EMG groups. chronic heart disease is coronary artery disease. Athero-
sclerosis is the principle cause of vascular lesions of the
Effects of perilla oil on hs-CRP, PAI-1 and TNF-α coronary artery and gradually develops to coronary ar-
The results of Table 1-2 indicate that: 1) exercising and tery disease. The highest rate of morbidity and mortali-
taking perilla oil can regulate plasma lipid levels, ty in patients with coronary artery disease is seen in
hs-CRP, PAI-1 and TNF-α; 2) there is a significant dif- those patients with hyperlipidemia. Hyperlipidemia is
ference between EG, MG and EMG; 3) the levels of an important risk factor contributing to coronary ar-
Table 1 Level of blood lipids at different times (mmol/L, xˉ ± s )
Time
Group n TC TG HDL-C LDL-C
(week)
EG 0 12 6.2±0.8ab 3.4±0.9ab 1.4±0.4ab 3.9±0.8ab

MG 0 12 6.2±0.8 3.3±0.8 1.4±0.4 3.9±0.8

EMG 0 12 6.2±0.7 3.4±0.8 1.4±0.4 4.0±0.8

EG 4 12 5.7±0.7c 3.2±0.8c 1.5±0.4b 3.5±0.9

MG 4 12 5.8±0.7 3.2±0.8 1.5±0.5 3.5±0.8

EMG 4 12 5.6±0.6 3.1±0.6 1.6±0.6 3.5±0.7

EG 8 12 5.5±0.6 3.1±0.7 1.5±0.5 3.2±0.7

MG 8 12 5.5±0.5 3.0±0.8 1.6±0.6 3.2±0.7

EMG 8 12 5.3±0.9 2.8±0.7 1.6±0.6 3.1±0.7


Notes: EG: exercise groups; MG: medicine group; EMG: exercise and medicine group; TC: total cholesterol; TG: triglyceride; HDL-C:
high density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol. aP<0.05 compared with the datum in the same group
after 4 weeks; bP<0.05 compared with the datum in the same group after 8 weeks; cP>0.05 compared with the datum in the same group
after 4 weeks.

JTCM | www. journaltcm. com 172 April 15, 2013 | volume 33 | Issue 2 |
Wei MG et al. / Clinical Study

Table 2 Level of the cell factors at different times ( xˉ ± s )


Time hs-CRP PAI-1 TNF-α
Group n
(week) (mg/L) (ng/mL) (ng/mL)
EG 0 12 3.41±0.63a 38.87±6.18a 1.21±0.19a
MG 0 12 3.38±0.55 39.24±6.23 1.23±0.24

EMG 0 12 3.43±0.58 37.79±5.98 1.23±0.19

EG 8 12 2.74±0.53 33.56±5.88 0.97±0.18

MG 8 12 2.77±0.61 34.19±6.12 0.94±0.22

EMG 8 12 2.76±0.54 33.89±5.93 0.88±0.21


Notes: EG: exercise groups; MG: medicine group; EMG: exercise and medicine group; hs-CRP: highly sensitive C-creative protein; PAI-1:
plasminogen activator inhibitor-1; TNF-α: tumor necrosis factor-α. aP<0.05 as compared with the datum in the same group after 8 weeks.
Table 3 Saftey index levels before and after the study ( xˉ ± s )
Time WBC ALT Scr
Group
(week) (a109/L) (μ/L) (mmol/L)
EG 0 7.6±2.1b 22.5±10.9b 64.2±13.2b

MG 0 7.0±1.5 24.2±9.8 67.3±13.0

EMG 0 7.14±2.1 23.6±11.0 66.3±13.1

EG 8 6.7±1.4 24.5±14.2 62.4±11.2

MG 8 7.0±1.6 26.4±12.2 65.2±8.0

EMG 8 8.2±1.6 25.8±15.2 64.3±8.8


Notes: EG: exercise groups; MG: medicine group; EMG: exercise and medicine group; WBC: white blood cells; ALT: alanine
aminotransferase; Scr: serum creatinine. aP>0.05 as compared with the datum in the same group after 4 weeks; bP>0.05 as compared with
the datum in the same group after 4 weeks.
tery disease and subsequent myocardial infarction. PAI-1 is produced and secreted by endothelial cells.
The formation of atherosclerosis shows a complicated PAI-1 combine with tissue plasminogen activator (tPA)
pathological course. The metabolic disorder lipidemia to form the composition in blood. So PAI-1 could in-
can lead to the development of atherosclerosis. Endo- hibit tPA to resolve the fibrin. The normal lexel of
thelial cells are the target cells of lipidemia. Endothelial PAI-1 and tPA may determine the balance between he-
cells form a barrier between blood and smooth muscle mostasia and thrombosis. Damage to endothelial cells
cells of blood vessels. Endothelial cell involvement in the may cause these cells to secret PAI-1, increasing the lev-
formation of atherosclerosis has been reported,13,14and els of PAI-1 in the blood. In turn, high levels of PAI-1
damage to endothelial cells has been recognized as be- may inhibit tPA from resolving fibrin accumulation,
ing a precursor to the formation of atherosclerosis.15 It which will let the form of thrombosis easily than nor-
is therefore very important to maintain intact endothe- mal. Levels of PAI-1 in the sera could therefore be used
lial cells to prevent the formation of atherosclerosis. as a marker to evaluate whether endothelial cells are
High blood pressure can also contribute by damaging damaged or not. However, PAI-1 is also one of the
blood vessels and endothelial cells. acute reaction proteins, and its active function could in-
Clinical trials with fibric acid derivatives have demon- crease the incidence rate at some kinds of cardiovascu-
strated an improvement in cardiovascular end points lar disease.19
and coronarystenosis.16 These direct vascular effects TNF-α is a cell signaling factor which is produced and
may contribute to cardiovascular event reduction and secreted by many cells, including natural killer cells
explain the clinical benefits observed in these trials. and T cells. TNF-α can induce the expression of endo-
Endothelial dysfunction associated with metabolic syn- thelial cell adhesion molecules. TNF-α can also induce
drome and other insulin-resistant states are character- endothelial cells to secrete platelet-derived growth fac-
ized by impaired nitric oxide release from endotheli- tor, and improves the proliferation of endothelial and
um.17 Improvement in endothelial function is therefore smooth muscle cells of blood vessels. Endothelial cells
predicted to improve insulin sensitivity. This may be have a receptor for TNF-α, making endothelial cells
one mechanism by which fenofibrate decreases the inci- one of the target cells of TNF-α. This may be why
dence of coronary heart disease. TNF-α can hurt EC in the blood vessel. The higher
Excessive body fat is frequently associated with dyslip- the TNF-α level, the more severe the damage to endo-
idemia, metabolic syndrome and atherosclerotic vascu- thelial cells will be. There appears to be a direct ratio
lar diseases.18 between damage to an artery and the formation of ath-

JTCM | www. journaltcm. com 173 April 15, 2013 | volume 33 | Issue 2 |
Wei MG et al. / Clinical Study

erosclerosis. 3143-3421.
Inflammation plays a major role in the various stages 2 Baseline serum cholesterol and treatment effect in the
of atherosclerosis, from development of the initial fatty Scandinavian simvastatin survival study (4S). Lancet
streak, to plaque rupture, to resultant thrombosis. Cur- 1995; 345(8960): 1274-1275.
rent prevention and treatment guidelines for coronary 3 Influence of pravastatin and plasma lipids on clinical
artery disease depend on the assessment of an individu- events in the west of Scotland coronary prevention study
al's risk of cardiovascular events using algorithms such (WOSCOPS). Circulation 1998, 97(15): 1440-1445.
as the Framingham risk model. An accurate estimate of 4 Jukema JW, Bruschke AV, van Boven AJ, et al. Effects of
lipid lowering by pravastatin on progression and regression
the cardiovascular risk is therefore of paramount impor-
of coronary artery disease in symptomatic men with nor-
tance.
mal to moderately elevated serum cholesterol levels. The
The association between CRP and coronary artery dis-
regression growth evaluation statin study (REGRESS). Cir-
ease was first described more than two decades ago.20,21
culation 1995; 91(10): 2528-2540.
Since then, CRP has been the focus of intense investi-
5 Maron DJ, Fazio S, Linton MF. Current perspectives on
gation and has been proposed as an important and in- statins. Circulation 2000; 101(2): 207-213.
dependent risk factor for coronary artery disease. Mea- 6 Li JJ, Li YS, Chu JM, et al. Changes in plasma inflamma-
surement of CRP is thought to further aid risk assess- tory markers after withdrawal of statin therapy in patients
ment by stratifying individuals classified at an interme- with hyperlipidemia. Clin Chim Acta 2005; 366(12):
diate risk level.22,23 CRP levels are related to cardiovascu- 269-273.
lar disease. CRP levels will be higher with the develop- 7 Li JJ, Fang CH, Qian HY, Hu WL. Time course of rapid
ment of cardiovascular disease. CRP is associated with Creactive protein reduction by pravastatin in patients with
atherosclerosis through its stimulation of endothelial stable angina. Angiology 2006; 57(1): 1-7.
cells.24 Recent studies have suggested that hs-CRP is 8 Raison J, Rudnichi A, Safar ME. Effects of atorvastatin
more effective at forecasting heart events than ordinary on aortic pulse wave velocity in patients with hypertension
CRP.25 Some studies have suggested that hs-CRP is one and hypercholesterolaemia: a preliminary study. J Hum
of the markers which indirectly demonstrate the degree Hypertens 2002; 16(10): 705-710.
of cardiovascular disease.26-29 9 Shinohara K, Shoji T, Kimoto E, et al. Effect of atorvas-
Perilla oil is extracted from seeds of herbs of the genus tatin on regional arterial stiffness in patients with type 2 di-
Perilla. Perilla oil can regulate vital energy, disperse abetes mellitus. J Atheroscler Thromb 2005; 12(4):
phlegm, degrade blood fat and promote blood circula- 205-210.
tion; and is used in the treatment of patients with high 10 Wei MG, Xiong PH, Zhang L, Chen AP, Fei M, Li FL. Ef-
blood fat and showing symptoms such as cerebaria, fect of Perilla Oil Capsule on hyperlipidemia in patients
chest distress, disgorging sputamentum and extremity with syndrome of turbid phlegm obstruction. Zhong
numbness. Cheng Yao 2011; 33(9): 1476-1478.
Both the level of CRP and endothelial function inti- 11 Hu DY. How to protect and treat the abnormal blood
mately related to AS, there maybe liner correlation plasma in clinical. Shanghai: TongJi University Press 2006,
10: 66.
among them. The higher the CRP level, the more se-
12 The Co-committee of the guideline of protecting and
vere the endothelial function and the more obvious ath-
treating the high blood plasma for Chinese adult. The
erosclerosis will be. The level of CRP may therefore de-
guideline of protecting and treating the high blood plasma
termine the condition of atherosclerosis. Perilla oil, as a
for Chinese adult. Zhong Hua Xin Xue Guan Bing Za Zhi
single therapy, can reduce CRP levels. Endothelial func-
2007; 35 (5): 390-419.
tion (assessed with forearm blood flow) has shown im- 13 Ross R, Glomset JA. The pathogenesis of atherosclerosis.
provement following sole use with perilla oil.10,30 N Engl J Med 1976; 295(7): 369-377.
The results of this study suggest that exercising and tak- 14 Ross R. Atherosclerosis: current understanding of mecha-
ing perilla oil in combination can regulate plasma lipid nisms and future strategies in therapy. Transplant Proc
and CRP levels, PAI-1 and TNF-α more effectively 1993; 25(2): 2041-2043.
than either one individually. It is also suggested that pe- 15 Ross R. The pathogenesis of atheroselerosis: a perspective
rilla oil can protect endothelial cells and reduce the pos- for the 1990s. Nature 1993; 362: 801-809.
sibility of the development of atherosclerosis. Perilla oil 16 Rubins HB, Robins S J, Collins D, et al. Gemfibrozil for
has also shown a good safety coefficient throughout the secondary prevention of coronary heart disease in men
this study. with low levels of high-density lipo-protein cholesterol.
Veterans Affairs High-Density Lipoprotein Cholesterol In-
tervention Trial Study Group. N Engl J Med 1999; 341:
REFERENCES 410-418.
17 Vincent MA, Montagnani M, Quon MJ. Molecular and
1 Third Report of the National Cholesterol Education Pro- physiologic actions of insulin related to production of ni-
gram (NCEP) Expert panel on detection, evaluation and tricoxide in vascular endothelium. Curr Diab Rep 2003;
treatment of high blood cholesterol in adults (Adult Treat- 3: 279-288.
ment Panel III) final report. Circulation 2002; 106(25): 18 Kumada M, Kihara S, Sumitsuji S, et al. Coronary artery

JTCM | www. journaltcm. com 174 April 15, 2013 | volume 33 | Issue 2 |
Wei MG et al. / Clinical Study

disease: association of hypoadiponectinemia with coronary lar endothelial function. Heart 2004; 90(7): 750-754.
artery disease in men. Arterioscler Thromb Vasc Biol 25 George J, Goldstein E, Abashidze S. Circulating endothe-
2003; l23: 85-89. lial progenitor cells in patients with unstable angina; associ-
19 Wiman B, Hamsten A. The fibrinolytic enzyme system ation with systemic inflammation. Eur Heart J 2004; 25
and its role in the etiology of thromboembolic disease. (12): 1003-1008.
Semin Thromb Hemost 1990; 16(3): 207-216. 26 Berk B, Weintraub W, Alexander R. Elevation of C-reac-
20 Vigo C. Effect of C-reactive protein on platelet-activating tive protein in active coronary artery disease. Am J Cardiol
factorinduced platelet aggregation and membrane stabiliza- 1990; 65 (3): 168-172.
tion. J Biol Chem 1985; 260 (6): 3418. 27 Cook NR, Buring JE, Ridker PM. The effect of including
21 Volanakis J, Narkates A. Binding of human C4 to C-reac- Creactive protein in cardiovascular risk prediction models
tive proteinpneumococcal C-polysaccharide complexes for women. Ann Intern Med 2006; 145(1): 21.
during activation of the classical complement pathway. 28 Ridker PM, Buring JE, Shih J, et al. Prospective study of
Mol Immunol 1983; 20(11): 1201-1207. C-reactive protein and the risk of future cardiovascular
22 Zhang Y, Cliff W, Schoefl G, Higgins G. Coronary events among apparently healthy women. Circulation
C-reactive protein distribution: its relation to develop- 1998; 98(8): 731-733.
ment of atherosclerosis. Atherosclerosis 1999; 145(2): 29 Ridker PM, Hennekens CH, Buring JE, et al. C-reactive
375-379. protein and other markers of inflammation in the predic-
23 Nordestgaard BG, Zacho J. Lipids, atherosclerosis and tion of cardiovascular disease in women. N Engl J Med
CVD risk: is CRP an innocent bystander? Nutr Metab 2000; 342(12) : 836-843.
Cardiovasc Dis 2009; 19(8): 521-524. 30 Xu ZH, Shao YF, Zhu GH. Influence of perilla oil on rats'
24 Teragawa H, Fukuda Y, Matsuda K. Relation between C blood lipid and blood rheology. Ying Yang Za Zhi 1997;
reactive protein concentrations and coronary microvascu- 19(1): 11-15.

JTCM | www. journaltcm. com 175 April 15, 2013 | volume 33 | Issue 2 |

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