title: Sirt3 is essential for apelin-induced angiogenesis in post-myocardial infarction of diabetes.
abstract: 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 (Sirt3KO) 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/VEGFR2 expression together with increased myocardial vascular densities in WT-STZ+MI mice, but these alterations were not observed in Sirt3KO-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 Sirt3KO mice. APLN gene therapy increases angiogenesis and improves cardiac functional recovery in diabetic hearts via up-regulation of Sirt3 pathway.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Xuwei
authors.initials: X
authors.lastname: Hou
authors.forename: Heng
authors.initials: H
authors.lastname: Zeng
authors.forename: Xiaochen
authors.initials: X
authors.lastname: He
authors.forename: Jian-Xiong
authors.initials: JX
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D054392:Adipokines; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D000073861:Apelin; D017209:Apoptosis; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism; D015316:Genetic Therapy; D006334:Heart Function Tests; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D056566:Sirtuin 3 / Q000172:deficiency / Q000378:metabolism*; D014463:Ultrasonography
chemical_list: D054392:Adipokines; D043925:Angiogenesis Inducing Agents; D000073861:Apelin; C402826:Apln protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C525046:Sirt3 protein, mouse; D056566:Sirtuin 3
keywords: angiogenesis; apelin; apoptosis; diabetes; myocardial infarction; sirtuin 3