Association Of Serum Osteoprotegerin And Insulin-like Growth Factor-1 With Carotid Plaque In Aging Coronary Heart Disease Patients

Objective: Atherosclerosis (AS) is a kind of systemic disease, as the change of life style happened, incidence rate of coronary heart disease (CHD) presented an increased tendency. To use color Doppler to detect carotid artery atherosclerosis has been thought highly of increasingly. Recently, it has been found that there is a compacted relationship between carotid artery atherosclerosis and coronary artery scleratheroma, carotid artery atherosclerosis could be an independent risk factor of predicting CHD.Osteoprotegerin (OPG) is a newly discovered glycoprotein that is involved in the process of bone absorption. It can inhibit osteoclasts differentiation and development. OPG mRNA distributes extensively in tissues, it is expressed at high concentrations in liver,heart,lung,kidney,stomach,small intestine,skin,brain,spinal cord and skeleton. Many kinds of cytokines,hormones regulate its production and expression. OPG is also expressed in the angiocellular, including vascular smooth muscle cells (VSMCs) and endotheliocytes, normal vessel wall and early AS site also have its immunological activity. OPG is also a receptor for the cytotoxic ligand TNF-related apoptosis inducing ligand (TRAIL), OPG might have an effect on anti-apoptosis in endotheliocytes by inhibiting TRAIL-induced apoptosis of vascular cells. Endotheliocytes have the barrier function, while their life span is changed, the cells function disorder would happen, and then followed AS. The increase of serum OPG concentrations shows that endotheliocytes and VSMCs increase the expression of OPG to repair calcification of scleratheroma plaque. OPG could induce matrix metalloproteinase-9 activity in macrophages and smooth muscle cells, it may modulate matrix metalloproteinase-9 production in vascular cells, high OPG concentrations could be responsible for a number of changes within the atherosclerotic plaque that would promote plaque instability and favor plaque rupture.Insulin-like growth factor-1 (IGF-1) can stimulate accrementition and differentiation of epiphyseal plate chondrocytes, inhibiting collagenous degradation. IGF-1 is important to skeleton formation. IGF-1 is also present in cardiovascular system, endotheliocytes,smooth muscle cells and macrophages can synthesize and secrete IGF-1 and reciprocal receptor and conjugated protein. IGF-1 can promote smooth muscle cells proliferation and immigration, inhibit apoptosis. It is significant in atherosclerotic formation,development and blood vessel restenosis. Study confirmed that oxidative-LDL made local IGF-1 decreased, inhibited VSMCs proliferation and promoted their apoptosis, accordingly caused artery plaques and AS formation. Now it has been identified that lipid metabolic disorder is a risk factor of development of AS and plaque formation. IGF-1 has a similar function of insulin, its decrease also can make blood glucose and blood fat increased, promoting AS process.Association of serum OPG and IGF-1 with carotid artery plaque in aging CHD patients was rarely studied. It was found that rhIGF-1 could promote the expression of OPG mRNA in osteoblasts. By determining serum OPG and IGF-1 contents of CHD, compared with control group. The purpose is to investigate the association of serum OPG and IGF-1 with carotid plaque and whether they could be indexes of AS and plaque stability.Methods: 84 aging CHD patients were selected in hospital from September, 2005 to December, 2006. Among them there were 44 with stable angina pectoris (SAP) and 40 with acute coronary syndrome (ACS). 31 hospitalized patients without history of CHD were selected as control subjects. The diagnosis standard of acute myocardial infarction was followed as world health organization, unstable stable angina pectoris and SAP were followed as American College of Cardiology/ American heart association. Carotid ultrasound was applied to observe intima-media thickness (IMT),plaque formation and its hardness of hibateral common carotid artery,carotid bifurcate,subterminal internal carotid artery and external carotid artery. According to the echo intensity,plaques were divided into soft plaque,mixed plaque and hard plaque, meanwhile all kinds of plaque scores and total plaque score were recorded. Blood samples were collected, serum OPG and IGF-1 content was detected with enzyme linked immunosorbent assay (ELISA) after centrifugalization. Biochemical indicators such as serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-c),low density lipoprotein cholesterol (LDL-c),calcium(Ca),phosphorus (P),alkaline phosphatase (ALP),blood glucose(BGlu) and fibrinogen(Fg) were detected by biochemistry instrument. The results of experiments were expressed with mean±standard deviation ( x±s) in using the one-way ANOVA, LSD-t tests were used between two groups.Х2 test was used in counting data. Linear correlation of serum OPG,IGF-1 and carotid IMT,plaque scores and other risk factors were analyzed. Significance was set at P<0.05.Results: 1. Serum OPG concentrations were remarkably increased in ACS group, the differences were remarkable compared with SAP group and control group; serum OPG concentrations in SAP group were higher than control group, the difference between two groups was significant. Serum IGF-1 concentrations were remarkably decreased in ACS group, the differences were remarkable compared with SAP group and control group; serum IGF-1 concentrations in SAP group were lower than control group, there was a significant difference. 2. Soft plaque score,total plaque score and carotid IMT were much higher in ACS group, the differences were remarkable compared with SAP group and control group; soft plaque score,total plaque score and IMT in SAP group were higher than control group, the difference between two groups was significant. Mixed plaque score and hard plaque score in SAP group and ACS group were much more than control group, there were significant differences. 3.Linear correlation revealed that serum OPG had a positive correlation with Fg, serum IGF-1 had a negative correlation with TC,TG,LDL-c.Conclusions:1. Compared with control group, serum OPG concentrations increased obviously in SAP group and ACS group, and serum IGF-1 concentrations decreased obviously in SAP group and ACS group. It indicated that high serum OPG concentrations and low IGF-1 concentrations played a certain role in the process of CHD.2. Serum OPG concentrations had a positive correlation with carotid artery IMT and total plaque score respectively, while IGF-1 had a negative one, which indicated that the degree of AS increased and the development of plaque accelerated with increased serum OPG concentrations and decreased IGF-1 concentrations. Serum OPG and IGF-1 concentrations had positive and negative correlation with soft plaque score respectively. Soft plaques are unstable plaques, high OPG concentrations and low IGF-1 concentrations might make plaques more unstable.3. Serum OPG had a positive correlation with Fg, it could upregulate Fg, which might be important in the process of soft plaque formation. Serum IGF-1 had negative correlations with TC,TG and LDL-c, which meant IGF-1 might have an effect on lipid metabolism. It might had an effect with lipid on the process of AS and plaque formation.4. Doing ultrasonic inspection regularly and detecting serum lipid,OPG and IGF-1 in the meantime is to know the situation of carotid IMT and plaque. It could be significant to prevent and cure AS and CHD in earlier period, decreasing cardiovascular and cerebral vessel incidents.