title: Mitofusin 2 inhibits angiotensin II-induced myocardial hypertrophy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Cardiology, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education, Beijing, PR China.
authors.forename: Haiyi
authors.initials: H
authors.lastname: Yu
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Guo
authors.forename: Lin
authors.initials: L
authors.lastname: Mi
authors.forename: Xueying
authors.initials: X
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000503:physiopathology*; D020558:GTP Phosphohydrolases; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D051057:Proto-Oncogene Proteins c-akt; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat