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Atorvastatin reduces myocardial fibrosis in a rat model with post-myocardial infarction heart failure by increasing the matrix metalloproteinase-2/tissue matrix metalloproteinase inhibitor-2 ratio.
MedLine Citation:
PMID:  23769575     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: The cholesterol-lowering statin drugs have some non-lipid-lowering effects, such as inhibiting myocardial remodeling. However, the underlying mechanism is still unclear.
METHODS: The left anterior descending coronary artery was ligated to establish a rat model of heart failure, and the rats were divided into a sham operation (SO) group, myocardial infarction model (MI) group, and MI-atorvastatin group. Changes in hemodynamic parameters were recorded after the final drug administration. Histological diagnosis was made by reviewing hematoxylin and eosin (HE) stained tissue. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expressions of type I and type III collagen, matrix metalloproteinase-2 (MMP-2), and tissue matrix metalloproteinase inhibitor-2 (TIMP-2). Further, primary rat cardiac fibroblasts were cultured and the MTT assay was performed to determine the effect of atorvastatin on cardiac fibroblast proliferation.
RESULTS: The model of heart failure was established and the results of HE staining and Masson's trichrome staining revealed that the rats in the heart failure group showed obvious hyperplasia of fibrotic tissue, which was significantly reduced in the atorvastatin group. Real-time quantitative PCR showed that the MI group showed a significantly increased expression of type I and type III collagen, MMP-2, and TIMP-2, but a significantly reduced MMP-2/TIMP-2 ratio. Compared with the MI group, the atorvastatin group showed significantly reduced expression of type I and III collagen, unchanged expression of MMP-2, significantly reduced expression of TIMP-2, and an increased MMP-2/TIMP-2 ratio. We further found that atorvastatin significantly inhibited the Ang II-induced fibroblast proliferation and the expression of type I and type III collagen in cardiac fibroblasts while increasing the MMP-2/TIMP-2 ratio.
CONCLUSIONS: These data suggest that atorvastatin can inhibit cardiac fibroblast proliferation and enhance collagen degradation by increasing the MMP-2/TIMP-2 ratio, thereby inhibiting the formation of myocardial fibrosis in rats with heart failure after myocardial infarction.
Authors:
Zhe An; Guang Yang; Yu-Quan He; Ning Dong; Li-Li Ge; Shu-Mei Li; Wen-Qi Zhang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chinese medical journal     Volume:  126     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  2149-56     Citation Subset:  IM    
Affiliation:
Department of Cardiology, the Second Hospital, Jilin University, Changchun, Jilin 130041, China.
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