Arshad Noori Ghani Al-Dujaili, and Wijdan Rajh Hamza Al-Kraity
Biology Department, Faculty of Sciences, University of Kufa, Iraq
*Corresponding Author E-mail: arshad.aldujaili@uokufa.edu.iq
ABSTRACT:
In the current study, Seventy menopausal women have CHD were admitted to the Coronary Care Unit of AL-Sadder Teaching Hospital in AL-najaf AL-Ashraf during the period from January to April/2016 for the ages were ranging from 40 to 69 years old. The samples were divided into three groups (SA 25, UA 22, AMI 23), while the healthy group was composed of 20.The current study indicated a significant increase(p<0.05) in serum CD147 of CHD compared with healthy group, while a significant decrease (P<0.05)in serum E2 concentration of CHD compared with healthy group. The results also revealed a significant increase (p>0.05)of serum CD147concentration in AMI group as compare with UA group and SA group of CHD, While serum of E2 concentration showed a significantly decrease (p<0.05)in AMI compare with UA and SA groups of CHD. The result showed also a negative correlation between E2 and CD147.
KEYWORDS: Coronary heart disease, Menopause, Estradiol and CD147.
1. INTRODUCTION:
Coronary heart disease (CHD) (also known as coronary artery disease or ischemic heart disease) is the most common form of heart disease and results from atherosclerosis, or the accumulation of fatty plaques in artery walls that cause narrowing of the artery lumen1. Menopause is a risk factor for coronary heart disease because estrogen withdrawal detrimental effect on cardiovascular function and metabolism the menopause compounds many cardiovascular disease risk factors including changes in body fat distribution, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, endothelial dysfunction, and vascular inflammation2-5. Estradiol (E2) is known to relax arteries directly via endothelial NO and thus exert potential anti-atherogenic effects6. Also, estradiol prevents early atheroma through endothelial-mediated mechanisms7.
Estrogen exerts its anti-inflammatory effects on the vasculature through different mechanisms such as direct antioxidant effect, generation of nitric oxide, prevention of apoptosis in vascular cells and suppression of cytokines and the renin-angiotensin system 8,9.
CD147 is a 57-kDa glycosylated transmembrane immunoglobulin that is also called extracellular matrix metalloproteinase inducer (EMMPRIN), CD147 is capable of homotypic binding which can lead to platelet degranulation upon platelet binding and stimulation of the nuclear factor kappa B (NF-κB) pathway in monocytes, which lead in turn to the production of matrix metalloproteinase (MMP) and cytokines, specifically MMP-9, TNF-α and IL-610,11.
The study of Yurchenkoetal.12 recognized the CD147 act as a surface receptor for extracellular CYP-A, former studies with mutant CYP-A proteins indicate that CYP-A is able to induce chemot axis and signaling by two different pathways: (i) extracellular binding to CD14713 and (ii) Peptidylprolyl cistransisomerase (PPiase) activity12.
MATERIALS AND METHODS:
Patients and healthy groups Seventy patients were divided into three study groups:
Acute myocardial infarction patients group included 23 subjects, unstable angina patients group included 22 subjects and stable angina patients group included 25 subjects, the control group was composed of twenty healthy women. The samples were collected from the Coronary Care Unit (CCU) in Al-Sadder Teaching City in AlNajafprovince/ Iraq, during the period from January till April,2016. The ages of patients and control were ranging from 40 to 69 years old.
Collection of blood samples:
Five milliliters of venous blood samples were drown using a disposable needle and plastic syringes from each patients and controls subject. Blood was left at room temperature for 10 minutes to clot, centrifuged 6000 rpm for 10 minutes, and then serum was separated and transported into new disposable tubes.
Biochemical markers:
Specific kit for measurement human estradiol concentrations in serum was supplied by (AccuBind™., Monobind Inc. USA-Catalog No. 4925-300).
· Determination of serum CD147 level:
Specific kit for measuring human CD147 concentrations in serum was supplied by Elabscience Biotechnology Co., Ltd. A Catalog No: E-EL-H1606.
Statistical Analysis:
The data of present study were articulated as (Mean ± Standard Error), the statistical analysis (descriptive statistics, Correlation coefficients, pvalue) were calculated by using megastat and Graphpad prism, when P value<0.05 was statistically asignificant14.
RESULTS:
· Comparison of lipid profile between coronary heart disease CHD and healthy group in menopausal women.
The result in table (1) exhibit significant decrease (p<0.05) in serum level of E2(4.338±0.147pg/ml) in CHD group compared with (11.449±0.271pg/ml) in HT group, while the results in the same table exhibit significant increase (p<0.05) in serum level of CD147 (1017±8.553pg/ml) in CHD group compared with (909.095±5.740pg/ml) in HT group.
Table (1): Comparison of Serum level lipid profile between CHD and HT group in menopausal women.
|
Groups Parameters |
Mean ±S.E. |
|
|
HT |
CHD |
|
|
E2 |
11.449±0.271pg/ml |
4.338±0.147pg/ml* |
|
CD147 |
909.095±5.740pg/ml |
1017±8.553pg/ml * |
(*) :Represent the significant differences at (p<0.05).
· Comparison of lipid profile between Stable-angina (SA), Unstable-angina(UA) and Acute myocardial-infarction(AMI) of CHD menopausal women.
The result in table (2) exhibit a significant decrease(p<0.05) in serum of E2 (3.136±0.212pg/ml) in AMI group and (4.290±0.158pg/ml) in UA group compared with (5.589±0.172pg/ml) in SA group of CHD. While the results in the same table showed there is a significant increase (p>0.05) of serum CD147 concentration in AMI group (1054.850±8.952pg/ml) as compare with UA group (1015.480±7.685pg/ml) and SA group (981.243±6.021pg/ml) of CHD.
Table (2): Comparison of Serum level lipid profile between SA, UA and AMI of CHD menopausal women.
|
Groups Parameters |
Mean ±S.E. |
||
|
SA |
UA |
AMI |
|
|
E2 |
5.589±0.172pg/ml a |
4.290±0.158pg/ml b |
3.136±0.212pg/ml c |
|
CD147 |
981.243±6.021pg/ml a |
1015.480±7.685pg/ml b |
1054.850±8.952pg/ml c |
The different letters (a,b,c):represent the significant differences at (p<0.05).
· The correlation estradiol with CD147:
The figure(1) indicated, there is a significant negative association (P<0.05, r = - 0.889) between CD147 and estradiol concentrations of CHD in menopausal women.
Figure (1): Correlation between serum estradiol and serum CD147 levels of CHD in menopausal women.
DISCUSSION:
The present study indicate a significant decrease(p>0.05)in serum level estradiol in CHD of menopausal decease in comparison of healthy group. The incidence of cardiovascular disease and hyperlipidemia increases with age in both the sexes, but in women the risk increases markedly after menopause 15. The average age of menopause is 50.5 yrs, but some women may enter menopause at earlier age. After menopause, as there is loss of ovarian functions and depletion of various ovarian hormones, these results in adverse changes in glucose and insulin metabolism, body fat distribution, lipid metabolism, coagulation, fibrinolysis and vascular endothelial dysfunction, because of the aging and menopausal effects, the women will enhance total body fat mass, favoring the central body fat dissemination. Age, menopause and central obesity were all independent and important factors to the cardiovascular disease risk factors in women 16-18.
The incidence of coronary heart disease in menopausal women correlated with decrease in estrogen level that may be affected of increased of vascular and platelet nitric oxide production since reduce vascular tone, platelet aggregation and vascular growth may explain why menopausal women have high prevalence of hypertension and atherosclerosis19. An assortment of factors can add to endothelial dysfunction, hypertension elevates the shear forces that cause chronic intimal injury which lead to the coronary endothelium mainly close bifurcations, that intimal injury permit for the lipid accumulation, macrophages and the source of the intimal plaque(LDL) which are the source of most lipids in atherosclerotic plaques 20.
The rupture in the plaque can create thrombosis and a complicated injury. This acute thrombus can make complete or incomplete occlusion that additionally diminishes blood stream to the myocardium when combined with vasospasm21. Microvascular disease or endothelial dysfunction or both perhaps add to diminished blood stream to the myocardium, The period and sternness of blood stream diminution determines the sternness of coronary disorder signs: (unstable angina) or myocardial infarction22.
The present study indicated a significant elevate(p<0.05) in serum CD147 concentration in coronary heart disease of menopausal women in comparison of healthy group.
The study of Seizer et al. 23 indicated that CD147 expression was elevated in the heart tissues of acute myocardial infarction patients in addition to in the left anterior descending artery ligation induced I/Rmice model. The study of Schmidt etal. 24 indicated that releasing of CD147 has at present been seen on the platelet surface, and its releasing was up regulated in vitro in response to platelet agonists, consisting of Adenosine diphosphate, thrombin and collagen.
Platelet CD147 was also a receptor for extracellular CYP-A, that assist in regulated chemo tactic responses for instance inflammation 25. Circulating concentrations of Matrix metalloproteinases are arise in SA and UA26,27. CD147 induce MMPs which play a critical role in vascular remodeling, because they regulate the degradation of the extracellular matrix whose remodeling is chiefly widespread in unstable plaques and the CD147 releasing may have a mainly chief role in unstable coronary artery disease.
The atherosclerosis is an inflammatory progressive disease of the vascular wall, the damage of the atherosclerotic plaque is considered a key process that starts acute myocardial infarction28. The vulnerability of plaques is described by the elevation of inflammatory cells and extracellular matrix metalloproteinase stimulate CD147 which damage the fibrouscap of the plaque29. The MMP9 is more releasing and secreted via activated monocytes, in the acute myocardial infarction and MMP9 it has been observed to be released into the plasma and consequently can be used as a marker of acute myocardial infarction30. The study of Seizer et al.31 indicated that CYP-A is applies an assortment of functions because of its peptidyl prolylcistrans isomerase (PPIase) action, when discharged in to the extracellular space, CYP-A links to its extracellular receptorCD147 and along these lines starts a cascade of inflammatory processes, that investigation demonstrate that both intra- and extra-cellular CYP-A notably contribute to cardiovascular inflammation, acute myocardial ischemia and reperfusion damage, and myocardial remodeling processes. therefore, CYP-A seems to stand for a novel target to treat vascular and myocardial inflammation.
CONCLUSION:
The present study concluded that E2 and CD147 were markers for detection and diagnosis of coronary heart disease in menopausal women.
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Received on 12.12.2017 Modified on 24.12.2017
Accepted on 20.01.2018 © RJPT All right reserved
Research J. Pharm. and Tech. 2018; 11(1): 317-320.
DOI: 10.5958/0974-360X.2018.00058.6