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The therapeutic effect of Rosuvastatin on cardiac remodeling from hypertrophy to fibrosis during the end-stage hypertension in rats.
MedLine Citation:
PMID:  22288611     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: End-stage hypertensive heart disease is an increasing cause of cardiac mortality. Therefore, the current study focused on the cardiac remodeling from hypertrophy to fibrosis in old-aged SHRs, and explored the therapeutic effects of Rosuvastatin and its possible mechanism(s) of action. METHODS: SHRs at age 52 weeks were randomly divided into three groups, the first two to receive Rosuvastatin at a dose of 20mg.kg(-1) .d(-1) and 40mg.kg(-1) .d(-1) , respectively, and the third to receive placebo, which was to be compared with Wistar-Kyoto as controls. After 2-month treatment, SBP, HW/BW% and echocardiographic features were evaluated, followed by H&E and Masson trichrome staining in conjunction with qPCR of fetal gene expressions. TUNEL assay and immunofluorescent labeling for active caspase-3 were used to detect the apoptotic cardiomyocytes. Signaling pathways involved were examined by western blot. RESULTS: Old-aged SHR developed end-stage hypertensive heart disease characterized by significant enhancement of HW/BW%, LVAWd and LVPWd, and decreased LVEF and LVFS, accompanied by cardiomyocytes enlargement and fibrosis along with activation of fetal gene program. Cardiac apoptosis increased significantly during the transition process. Rosuvastatin reduced hypertrophy significantly via AT(1) Receptor-PKCβ2/α-ERK-c-fos pathway; protected myocardium against apoptosis via Akt-FOXO1, Bcl-2 family and survivin pathways, and consequently suppressed the caspase-3 activity. CONCLUSION: The present study revealed that old-aged SHRs developed cardiac remodeling from hypertrophy to fibrosis via cardiac apoptosis during the end stage of hypertensive heart disease. These pathological changes might be the consequence of activation of AT(1) Receptor-PKCβ2/α-ERK-c-fos and AKT-FOXO1/Bcl-2/survivin/Caspase3 signaling. Rosuvastatin effectively attenuated the structural changes by reversing the signaling transductions involved. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Authors:
W B Zhang; Q J Du; H Li; A J Sun; C H Qiu; C N Wu; G Zhao; H Gong; K Hu; Y Z Zou; J B Ge
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-30
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  -     ISSN:  1582-4934     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Affiliation:
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Institute of Biomedical Science, Fudan University, Shanghai, 200032, China.
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