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Effect of pravastatin on cholesteryl esters in foam cells and the relation with caveolin--1

Qin Li, Qin Xuping, Wang Zuo, Zhu Bingyang, Liao Duanfang

Institute of Pharmacy and Pharmacology, Nanhua University.Hengyang 421001,Hunan；China

Abstract

The purpose of the present study was to investigate the effect of pravastatin on cholesteryl esters in foam cells of murine macrophages and the relation with caveolin-1. RAW 264.7 murine macrophages were coincubated with 80 mg/L oxidized low density lipoprotein （ox-LDL） and pravastatin （0--100#mu#mol FL） respectively for 24 h. When the best control concentration of pravastatin was confirmed, RAW 264.7 murine macrophages were coincubated with 80 mg/L ox-LDL and pravastatin of the best concentration respectively for 0, 6, 12, 24 h. Oil red O dyeing experiment was used to show the lipid droplets in foam cells. High performance liquid chromatography （HPLC） analysis was performed to determine the content of cellular cholesterol. The level of caveolin-1 was determined by Western blot analysis. The result showed that when macrophages were incubated with 80 mg/L ox-LDL, the ratio of cellular cholesteryl ester to total cholesterol （CE/TC） was beyond 50% through HPLC analysis, and a great deal of lipid droplets displayed in cells through Oil red O dyeing experiment, which manifested the formation of the foam cells. Pravastatin could decrease CE in foam cells in a concentration-dependent manner （1--100#mu#mol/L）. At the concentration of 100 #mu#mol/L, pravastatin decreased cellular CE more than 50%. The effects of pravastatin on the decrease of CE in murine macrophages also displayed a time-dependent manner （incubated with 100#mu#mol/L pravastatin from 6 to 24 h）. Moreover, the expression of caveolin-1 was decreased when the macrophages were incubated with ox-LDL （80 mg/L）, while treatment with pravastatin increased the level of caveolin-1 and displayed a concentration-and timedependent manner. These results suggest that pravastatin could inhibit the development of foam cells through the decrease of cellular CE, which may be related to the upregulation of caveolin-1.

Key words: pravastatin;caveolin-1;cholesteryl ester;macrophage;foam cells

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Citing This Article：

Qin Li, Qin Xuping, Wang Zuo, Zhu Bingyang, Liao Duanfang. Effect of pravastatin on cholesteryl esters in foam cells and the relation with caveolin--1. Acta Physiol Sin 2006; 58 (1): (in Chinese with English abstract).