Involvement Of Caveolin-1 In The Effect Of Pravastatin On The Inhibition Of The Foam Cell Formation Induced By Ox-LDL

Pravastatin is a kind of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol biosynthesis. However, the overall clinical benefits observed with statin therapy are greater than what might be expected from changes in lipid profile along. This suggests that the beneficial effects of statins may extend beyond their effects on serum cholesterol levels[1]. Experimental and clinical evidence indicates that some of the cholesterol-independent effects of statins involve (1) endothelial normalization of nitric oxide production[2], (2) anti-inflammatory effects and inhibition of monocyte / endothelial cell adhesion[3], (3) inhibition of scavenger receptor expression[4], (4) strengthening of the fibrous cap[5], (5) inhibition of platelet thrombus formation/reduction of thrombotic response[7] and (6) inhibition of smooth muscle cell proliferation[7]. One of the earlist events in atherosclerotic plaque formation is the accumulation of lipid-laden foam cells derived from macrophages. Scavenger receptors are thought to play a significant role in atherosclerotic foam cell development because of their ability to bind and internalize modified lipids, such as oxidized LDL[8-9]. Caveolin-1, the marker protein of caveolae, is a principal component to maintain the structure and function of caveolae and appears to play a critical role in regulating the cholesterol concentration of caveolae and maintain cellular cholesterol homeostasis. However, Little is known about the change of caveolin-1 in the atherosclesis development ,and the possible mechanism of pravastatin descrease cholesteryl esters in foam cells . The present work aimed to investigate possible relation of Caveolin-1 and atherosclerosis, and indicate the possible mechanism of pravastatin descrease cholesteryl esters in foam cells.Part â… . The change of Caveolin-1 in the development of atherosclerosis in apoE-deficent miceAIM : Caveolin-1 is related to the intracellular cholesterol efflux. The objection of study is to observe the changes of caveolin-1 in the development of AS in apoE-deficient mice.METHODE : 40 male C57BL/6J mice and apoE-deficient mice were devidede into control group and apoE-def icient mice group, the latters were further divided into 3 subgroups dependent on the survival weeks(10,20,30 weeks). The serum total cholesterol, triglyceride, high and low desity cholesterol were determined. The areas of aortic wall and plaque lesion were calculated. Caveolin-1 was analysed by immunohistology and western-blotting.RESULTS : The serum levels of total cholesterol , triglyceride, and low desity cholesterol in the apoE-def icient mice were elevated significantly by comparing with those in the normal mice, as well as plaque areas and the ratio of plaque areas and aortic areas. But the expression of Caveolin-1 in aortic wall in the apoE-deficient mice is decreased by comparing with those in the normal mice.CONCLUSION :The expression of Caveolin-1 in aortic of apoE-deficient mice is decreased, which may be related with the atherositic formation.Part â…¡. Involvement of Caveolin-1 in the effect of pravastatin on the cellular cholesterol homeostasis.AIM: To investigate possible effection of Caveolin-1 on pravastatin...