Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet

Lipids in Health and Disease

Research

Guohua Song¹  Hua Tian¹  Yang Yu¹  Shucun Qin¹  Shutong Yao¹  Jia Liu²  Zhenmei Zhao³  Guoli Li³ 

[1] Institute of Atherosclerosis, Taishan Medical University, 271000, Taian, Shandong, China;Institute of Atherosclerosis, Taishan Medical University, 271000, Taian, Shandong, China;Medical College, Yangzhou University, 225009, Yangzhou, Jiangsu, China;Medical College, Yangzhou University, 225009, Yangzhou, Jiangsu, China;

关键词: Simvastatin;    Cholesterol Efflux;    Simvastatin Treatment;    LCAT Activity;    Scavenger Receptor Class;   

DOI  :  10.1186/1476-511X-10-8

 received in 2010-12-22, accepted in 2011-01-18,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundStatins are first-line pharmacotherapeutic agents for hypercholesterolemia treatment in humans. However the effects of statins on atherosclerosis in mouse models are very paradoxical. In this work, we wanted to evaluate the effects of simvastatin on serum cholesterol, atherogenesis, and the expression of several factors playing important roles in reverse cholesterol transport (RCT) in apoE-/- mice fed a high-fat diet.ResultsThe atherosclerotic lesion formation displayed by oil red O staining positive area was reduced significantly by 35% or 47% in either aortic root section or aortic arch en face in simvastatin administrated apoE-/- mice compared to the control. Plasma analysis by enzymatic method or ELISA showed that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) contents were remarkably increased by treatment with simvastatin. And plasma lecithin-cholesterol acyltransferase (LCAT) activity was markedly increased by simvastatin treatment. Real-time PCR detection disclosed that the expression of several transporters involved in reverse cholesterol transport, including macrophage scavenger receptor class B type I, hepatic ATP-binding cassette (ABC) transporters ABCG5, and ABCB4 were induced by simvastatin treatment, the expression of hepatic ABCA1 and apoA-I, which play roles in the maturation of HDL-C, were also elevated in simvastatin treated groups.ConclusionsWe demonstrated the anti-atherogenesis effects of simvastatin in apoE-/- mice fed a high-fat diet. We confirmed here for the first time simvastatin increased the expression of hepatic ABCB4 and ABCG5, which involved in secretion of cholesterol and bile acids into the bile, besides upregulated ABCA1 and apoA-I. The elevated HDL-C level, increased LCAT activity and the stimulation of several transporters involved in RCT may all contribute to the anti-atherosclerotic effect of simvastatin.

【 授权许可】

Unknown   
© Song et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.