Effect Of The Factors Related To Cholesterol Metabolism On The Occurrence And Development Of Atherosclerosis

Atherosclerosis (AS) is the pathologic background of many clinical cardiovascular diseases,and also is induced by many factors,through different links,but it's morbidit mechanism is still not distinctive. Cholesterol has been verified as the important cause of AS and cornary artery disease(CAD) by many elementary and clinical investigation. Serum cholesterol can damage vascular smooth muscle cell,macrophage and make these cells become foam cells,and also damage vascular endothelial cell to cause the formation of atherosclerotic plaque. A lot of first and second degree prevention trials such as LRC-CPPT HHS 4S CARE have proved that morbidity and mortality of myocardial infarction and cardiovascular disease can be decreased by lowing serum total cholesterol and low density lipoprotein cholesterol,but the factors related to cholesterol metabolism,including the production of cholesterol metabolism and key transfer protein during cholesterol metabolism have not been widely investigated.Objective:To confirm whether the product of cholesterol such as cholic acid and aldosterone can transform macrophages into foam cells,and investigate if the relationship of the key protein during cholesterol reverse transfer,ABCA1,with adherence factors.Methods:1) Macrophages in abdominal cavity of NIH mouse were cultivated in medium RPMI1640 with cholic acid or aldosterone. The changes of cell,organell and emerge of lipid droplet in the cell were observed under electron microscope. 2) Detect whether ABCA1 mRNA are expressed in ECV-304;the changes of mRNA and protein of ABCA1,ICAM-1,MCP-1 in ECV-304 after treated by 8-Br-cAMP were observed.Results:1) The proliferation of lysosome,damage of mitochondrion and rough endoplasmic reticulum,karyopyknosis,karyolysis,occurence of lipid droplets and formation of foam cells were caused by cholic acid andaldosterone.2) There are ABCA1 mRNA expression in ECV-304;the mRNA and protein expression of ABCA1 was increased and reached the peak value at 6 hour,12 hour,the changes of ICAM-1 and MCP-1 were similiry to that of ABCA1.Conclusions:l)Cholic acid and aldosterone participate the formation of AS by inducing occurrence of foam cells.2)In vascular endothelial cell,ABC A1,with ICAM-1 and MCP-1,may produce their effects in the occurrence of AS.