| Objective: 1. To explore the clinical relations among the serum level of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) with the severity of coronary atherosclerosis. The effect of AT1 receptor antagonist losartan on soluble adhesion molecules in individuals with coronary heart disease (CHD) was further evaluated. 2. To study the effect of losartan on the expression of vascular cell adhesion molecule-1 in rabbit model of high-cholesterol diet induced atherosclerosis and explore the role of angiotensin II in inflammation mechanisms of atherosclerosis.Methods: 1. Fifty eight normotensive patients with coronary heart disease (CHD) undergoing diagnostic coronary angiography were randomly selected. These patients were compared against a control population with no known coronary heart disease. The serum level of ICAM-1 and VCAM-1 were measured by enzyme-linked immunoadsprdent assay (ELISA) and the other inflammation markers, such us neutrophilic granulocyte account, Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were obtained by clinical routine methods. Relationships between levels of adhesion molecules and risk factors for atherosclerosis were evaluated and the differences among thelevels of circulating cellular adhesion molecules for the groups were also assessed. 2. Fifty eight patients were randomly divided into two groups, one was the control group receiving Isosorbide dinitrate 10mg tid and Betaloc 25 mg bid, the other was the group of Losartan receiving Isosorbide dinitrate lOmg tid, Betaloc 25mg bid and Losartan 50mg qd. Symptomatic and ECG improvement and side effects were observed. Blood samples were collected at 4, 8 weeks for measurement of levels of soluble adhesion molecules by ELISA and the levels of blood pressure were recorded. The effects of AT1 receptor losartan on soluble adhesion molecules in individuals with CHD were observed. 3. Eighteen male New Zealand white rabbits were randomly divided into negative control group, High-cholesterol group and Losartan group, each group consisting of six rabbits. The negative control group were fed with common diet, the high-cholesterol group were high-lipid fed (5% pig fat, 0.5% cholesterol) to establish atherosclerosis model, the Losartan group were fed high-lipid chow and losartan (25mg/kg/d). Before and after 8 weeks, the plasm level of angiotensin II were measured by Radioimmunoassay (RIA) and blood lipid were measured by enzyme method. After 8 weeks, the thickness of intima and media of aortas were assessed by light microscopy and computer. The expression of VCAM-1 was determined by immunohistochemical analysis and the expression of VCAM-1 mRNA was determined by in situ hybridization (ISH) and PT-PCR.Results: 1. The levels of sICAM-1 and sVCAM-1 in patients with coronary heart disease were significantly higher than those of health individuals (p<0.01). Other inflammation markers of patients were also higher in patients with coronary heart disease, but the differences had no statistic significance (p>0.05). A significantly correlation between the severity of the coronary artery lesions and the serum levels of ICAM-1 and VCAM-1 were found. It also showed serum levels of ICAM-1 and VCAM-1 relate significantly to TC and LDL. 2. Before treatment, the serum levels of sICAM-1 and sVCAM-1 had no significantly difference in patients of two groups. After treatment, the levels of sICAM-1 and sVCAM-1 in patients of Losartan group were significantly reduced at the four-week interval and the eight-week interval (p<0.01), on the other hand, the levels of sICAM-1 and sVCAM-1 in patients of control group were not significantly reduced at the four-week interval. Though the levels of sVCAM-1 in patients of control group were significantly reduced at the eight-week interval(p<0.01), the levels of sICAM-1 and sVCAM-1 in patients of Losartan group significantly lower than those of control group. 3. TC, TG, LDL were significantly elevated in the rabbits of high-cholesterol group and Losartan group aft...
|
PDF Full Text Request