Open AccessSirt3 is essential for apelin‐induced angiogenesis in post‐myocardial infarction of diabetes
Author(s) -
Hou Xuwei,
Zeng Heng,
He Xiaochen,
Chen JianXiong
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12453
Subject(s) - apelin , sirt3 , angiogenesis , diabetic cardiomyopathy , sirtuin , medicine , streptozotocin , endocrinology , myocardial infarction , diabetes mellitus , neovascularization , heart failure , biology , cardiomyopathy , receptor , enzyme , nad+ kinase , biochemistry
Heart failure following myocardial infarction ( MI ) is the leading cause of death in diabetic patients. Angiogenesis contributes to cardiac repair and functional recovery in post‐ MI . Our previous study shows that apelin ( APLN ) increases Sirtuin 3 (Sirt3) expression and ameliorates diabetic cardiomyopathy. In this study, we further investigated the direct role of Sirt3 in APLN ‐induced angiogenesis in post‐ MI model of diabetes. Wild‐type ( WT ) and Sirt3 knockout (Sirt3 KO ) mice were induced into diabetes by i.p. streptozotocin ( STZ ). STZ mice were then subjected to MI followed by immediate intramyocardial injection with adenovirus‐apelin (Ad‐ APLN ). Our studies showed that Sirt3 expression was significantly reduced in the hearts of STZ mice. Ad‐ APLN treatment resulted in up‐regulation of Sirt3, angiopoietins/Tie‐2 and VEGF / VEGFR 2 expression together with increased myocardial vascular densities in WT ‐ STZ + MI mice, but these alterations were not observed in Sirt3 KO ‐ STZ + MI mice. In vitro , overexpression of APLN increased Sirt3 expression and angiogenesis in endothelial progenitor cells ( EPC ) from WT mice, but not in EPC from Sirt3 KO mice. APLN gene therapy increases angiogenesis and improves cardiac functional recovery in diabetic hearts via up‐regulation of Sirt3 pathway.