Cargando…
Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet
BACKGROUND: Statins 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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031258/ https://www.ncbi.nlm.nih.gov/pubmed/21241519 http://dx.doi.org/10.1186/1476-511X-10-8 |
_version_ | 1782197336855805952 |
---|---|
author | Song, Guohua Liu, Jia Zhao, Zhenmei Yu, Yang Tian, Hua Yao, Shutong Li, Guoli Qin, Shucun |
author_facet | Song, Guohua Liu, Jia Zhao, Zhenmei Yu, Yang Tian, Hua Yao, Shutong Li, Guoli Qin, Shucun |
author_sort | Song, Guohua |
collection | PubMed |
description | BACKGROUND: Statins 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. RESULTS: The 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. CONCLUSIONS: We 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. |
format | Text |
id | pubmed-3031258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30312582011-02-01 Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet Song, Guohua Liu, Jia Zhao, Zhenmei Yu, Yang Tian, Hua Yao, Shutong Li, Guoli Qin, Shucun Lipids Health Dis Research BACKGROUND: Statins 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. RESULTS: The 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. CONCLUSIONS: We 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. BioMed Central 2011-01-18 /pmc/articles/PMC3031258/ /pubmed/21241519 http://dx.doi.org/10.1186/1476-511X-10-8 Text en Copyright ©2011 Song et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Research Song, Guohua Liu, Jia Zhao, Zhenmei Yu, Yang Tian, Hua Yao, Shutong Li, Guoli Qin, Shucun Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet |
title | Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet |
title_full | Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet |
title_fullStr | Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet |
title_full_unstemmed | Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet |
title_short | Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet |
title_sort | simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoe-knockout mice fed high-fat diet |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031258/ https://www.ncbi.nlm.nih.gov/pubmed/21241519 http://dx.doi.org/10.1186/1476-511X-10-8 |
work_keys_str_mv | AT songguohua simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet AT liujia simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet AT zhaozhenmei simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet AT yuyang simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet AT tianhua simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet AT yaoshutong simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet AT liguoli simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet AT qinshucun simvastatinreducesatherogenesisandpromotestheexpressionofhepaticgenesassociatedwithreversecholesteroltransportinapoeknockoutmicefedhighfatdiet |