Document Detail

Mitofusin 2 inhibits angiotensin II-induced myocardial hypertrophy.
MedLine Citation:
PMID:  21106870     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND OBJECTIVES: Myocardial hypertrophy is a common clinical finding leading to heart failure and sudden death. Mitofusin 2 (Mfn2), a hyperplasia suppressor protein, is downregulated in hypertrophic heart. This study examined the role of Mfn2 in myocardial hypertrophy and its potential signal pathway.
METHODS AND RESULTS: In in vitro studies, neonatal cardiac myocytes were isolated and cultured. Incubation of cultured cardiomycytes with angiotensin II (Ang II) inhibited gene expression of Mfn2; induced cell hypertrophy and protein synthesis; and activated protein kinase Akt. Pretreatment of cells with AdMfn2-a replication-deficient adenoviral vector encoding rat Mfn2 gene-upregulated Mfn2 expression and subsequently attenuated Ang II-induced cell hypertrophy; protein synthesis; and Akt activation. In in vivo studies, direct gene delivery of AdMfn2 into myocardium decreased the infusion of Ang II-induced atrial natriuretic factor (ANF, a hypertrophic marker) expression and cardiomyocyte cross-sectional area. Consistently, upregulation of Mfn2 in myocardium decreased the thicknesses of anterior and posterior walls of left ventricle (LV) and the ratio of LV mass/body weight in Ang II-treated rats. Of note, AdGFP (control for AdMfn2) did not affect the effects of Ang II in vitro or in vivo.
CONCLUSIONS: Upregulation of Mfn2 inhibits Ang II-induced myocardial hypertrophy. In this process, inhibition of Akt activation seems to play a significant role. These findings indicate Mfn2 is a critical protein in modulating myocyte hypertrophy.
Haiyi Yu; Yanhong Guo; Lin Mi; Xueying Wang; Lei Li; Wei Gao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-24
Journal Detail:
Title:  Journal of cardiovascular pharmacology and therapeutics     Volume:  16     ISSN:  1940-4034     ISO Abbreviation:  J. Cardiovasc. Pharmacol. Ther.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-10     Completed Date:  2011-09-02     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  9602617     Medline TA:  J Cardiovasc Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  205-11     Citation Subset:  IM    
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MeSH Terms
Angiotensin II / administration & dosage,  metabolism*
Animals, Newborn
Atrial Natriuretic Factor / metabolism
Cardiomegaly / physiopathology*
Gene Expression Regulation
Membrane Proteins / genetics,  metabolism*
Mitochondrial Proteins / genetics,  metabolism*
Myocytes, Cardiac / drug effects,  pathology*
Proto-Oncogene Proteins c-akt / metabolism
Rats, Sprague-Dawley
Reg. No./Substance:
0/Membrane Proteins; 0/Mitochondrial Proteins; 0/mitofusin 2 protein, rat; 11128-99-7/Angiotensin II; 85637-73-6/Atrial Natriuretic Factor; EC Proteins c-akt

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