Vascular endothelial growth factor-C protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis

• DOI: 10.1007/s11010-015-2622-9
• Publication Date: 2016-01-14T18:55:11Z
• Authors: Xu-guang Chen; Yan-xia Lv; Dan Zhao; Lei Zhang; Fei Zheng; Jian-Ye Yang; Xiao-lin Li; Lu Wang; Lin-Yun Guo; Ya-mu Pan; Yu-wen Yan; Shi-You Chen; Jia-Ning Wang; Jun-Ming Tang; Yu Wan
• Keywords: 0303 health sciences; Cardiotonic Agents; L-Lactate Dehydrogenase; Vascular Endothelial Growth Factor C; Apoptosis; Myocardial Reperfusion Injury; Hydrogen Peroxide; Recombinant Proteins; Cell Line; Rats; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; Malondialdehyde; Animals; Humans; Myocytes, Cardiac; Signal Transduction

VEGF-C is a newly identified proangiogenic protein playing an important role in vascular disease and angiogenesis. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. The objective of this study was to determine the role and mechanism of VEGF-C in myocardial ischemia-reperfusion injury. Rat left ventricle myocardium was injected with recombinant human VEGF-C protein (0.1 or 1.0 µg/kg b.w.) 1 h prior to myocardial ischemia-reperfusion (I/R) injury. 24 h later, the myocardial infarction size, the number of TUNEL-positive cardiomyocytes, the levels of creatine kinase (CK), CK-MB, cardiac troponin, malondialdehyde (MDA) content, and apoptosis protein Bax expression were decreased, while Bcl2 and pAkt expression were increased in VEGF-C-treated myocardium as compared to the saline-treated I/R hearts. VEGF-C also improved the function of I/R-injured hearts. In the H2O2-induced H9c2 cardiomyocytes, which mimicked the I/R injury in vivo, VEGF-C pre-treatment decreased the LDH release and MDA content, blocked H2O2-induced apoptosis by inhibiting the pro-apoptotic protein Bax expression and its translocation to the mitochondrial membrane, and consequently attenuated H2O2-induced decrease of mitochondrial membrane potential and increase of cytochrome c release from mitochondria. Mechanistically, VEGF-C activated Akt signaling pathway via VEGF receptor 2, leading to a blockade of Bax expression and mitochondrial membrane translocation and thus protected cardiomyocyte from H2O2-induced activation of intrinsic apoptotic pathway. VEGF-C exerts its cardiac protection following I/R injury via its anti-apoptotic effect.