Insulin-like Growth Factor-1 And Insulin Resistance And Coronary Angiography In Coronary Heart Disease

Cardiovarscular disease is No.l death causation of human being around the world. It is one of the commonest diseases in our country. The research field of cardiovascular disease in regard to growth hormone (GH) and its mitogenic mediator insulin-like growth factor-1 (IGF-1) has a long and distinguished history and is still intensively studied. The IGF-1 system includes the IGF-1,the IGF-1 receptor (IGF-1R),and multiple binding proteins. IGF-1 is synthesized in liver mainly, and also as a kind of paracrine and autocrine substance produced by endothelial cells and by vascular cells and cardiac myocytes. This growth factor system exerts multiple physiologic effects on the vasculature through both endocrine and autocrine/paracrine mechanisms. The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins which themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. A significant body of evidence has accmulated, indicating that expression of the components of the IGF system are regulated by multiple factors,including growth factors, cytokines, lipoproteins and hemodynamic forces. It has been established that IGF-1 facilitates glucose availability, increases sensitivity of general tissues, including normal and ischemic myocardium to insulin. Furthermore, IGF-1 promotes nitric oxide mediated vasodilation. There is accumulating evidence ofthe importance of IGF-1 in development of the vascular system. Still, mechanisms are insufficiently elucidated. In this study, we explore the link between cardiovascular disease and IGF-1.Insulin resistance is defined as a subnormal biological response to insulin exposure and may be observed at the cellular level or in intact tissues. Insulin resistance appears to be an important risk factor for coronary heart disease. Increasing evidence has linked insulin resistance with hypertension, obesity and dyslipidemia. The concurrence of these abnormalities has been coined the insulin resistance syndrome or the "metabolic syndrome". Because most of the research on insulin resistance has focused on the role in the pathophysiology of type 2 diabetes mellitus, there are little research on their relationship with heart disease, thus in the present we explore the link between cardiovascular disease and insulin resistance. Through coronary angiography we further investigate the relationship between insulin resistance and severity of coronary arterry stenosis.Methods: 44 patient who underwent coronary angiography were included in the study and divided into two groups according to extent of coronary artery stenosis: patients with coronary stenosis 50% were included in the group of coronary artery disease(CAD) (n=28) and patients with normal coronary artery or stenosis<25% as controls(n=16). In CAD group there were 18 patients with unstable angina pectoris(UAP) , 6 patients with acute myocardial infarction(AMI) and 4 patients with stable angina pectoris (SAP). Furthermore, the UAP subjects were separated into 2 parts by TIMI (the Thrombolysis in Myocardial Infarction) risk score: 10 patients with score 3 and 8 patients with score 2. The blood samples were taken intervenously from all subjects in the morning after hospitalization. The concentration of IGF-1 , insulin and blood glucose in all subjects studied were measured. 1SI was got according to the equation of ISI=LN[l/(FBIxFBG)]. The concentration of IGF-1 and ISI in each group was compared. The concentration of IGF-1 in the patients with UAP and TIMI risk score were correlativly analysized. The degree of coronary artery stenosis was assessed with angiographic imaging manipulation system and quantifiedin a modified Gensini score,which then were statistically correlated each other. The concentration of IGF-1 and ISI were undertook correlation analysis.Results: ?The concentration of IGF-1 in UAP and AMI group was significantly lower than that in control and SAP group (20.32±8.52,Mg/L, 14.03±2.80Jag/L vs 36.24±23.67//g/L, 29.31±4A3[ig/L, respectively) (P<0.01). There is no statistical difference between UAP and AMI group (P>0.05). There is no statistical difference between control and SAP group (P>0.05) too. (2) The ISI in both UAP and AMI group was significantly lower than that in control and SAP group (-4.39±0.11, -4.99±0.12 vs, -3.84±0.22, -3.96±0.09, respectively) (P<0.01). There is no statistical difference between control and SAP group (P>0.05). (3) The concentration of IGF-1 in UAP patients was negatively correlated with TIMI risk score (r=-0.678, P<0.01). (?According to the results of coronary angiography in subjects studied, ISI was negatively correlated with the degree of coronary artery stenosis (r=-0.389, P<0.05).(5)The concentration of IGF-1 is positively correlated with ISI (r=0.492, P < 0.01 ).Conclusion: 1. The concentration of IGF-1 in UAP and AMI group was significantly lower than that in control group, and the concentration of IGF-1 in UAP patients was negatively correlated with TIMI risk score, which indicates that the decrease of the IGF-1 concentration is a risk factor for coronary heart disease, and may be the predictor of ACS.2. The ISI in both UAP and AMI group was significantly lower than that in control group, and it was negatively correlated with the severity of coronary artery stenosis, which indicates that it may be the predictor of ACS and the extent of coronary artery stenosis.3 The concentration of IGF-1 is positively correlated with ISI, which means that IGF-1 can increase the sensitivity of body to insulin.4.The results in our study demonstrate that administration of exogenous IGF-1 will show us a new way for the treatment of ACS and Metabolism Syndrome.