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.
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Authors | Xuwei Hou, Heng Zeng, Xiaochen He, Jian-Xiong Chen |
Journal | Journal of cellular and molecular medicine
(J Cell Mol Med)
Vol. 19
Issue 1
Pg. 53-61
(Jan 2015)
ISSN: 1582-4934 [Electronic] England |
PMID | 25311234
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. |
Chemical References |
- Adipokines
- Angiogenesis Inducing Agents
- Apelin
- Apln protein, mouse
- Intercellular Signaling Peptides and Proteins
- Sirt3 protein, mouse
- Sirtuin 3
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Topics |
- Adenoviridae
(metabolism)
- Adipokines
- Angiogenesis Inducing Agents
(metabolism)
- Animals
- Apelin
- Apoptosis
- Cell Proliferation
- Diabetes Mellitus, Experimental
(complications, pathology, physiopathology)
- Endothelial Cells
(metabolism)
- Genetic Therapy
- Heart Function Tests
- Intercellular Signaling Peptides and Proteins
(genetics, metabolism, therapeutic use)
- Mice, Knockout
- Myocardial Infarction
(diagnostic imaging, etiology, physiopathology, therapy)
- Myocardium
(pathology)
- Neovascularization, Physiologic
- Sirtuin 3
(deficiency, metabolism)
- Ultrasonography
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