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

Abstract

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.

• 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
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 413 Issue 1-2 Pg. 9-23 (Feb 2016) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 26769665 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Recombinant Proteins
• VEGFC protein, human
• Vascular Endothelial Growth Factor C
• Malondialdehyde
• Hydrogen Peroxide
• L-Lactate Dehydrogenase

Topics

• Animals
• Apoptosis (drug effects)
• Cardiotonic Agents (administration & dosage, pharmacology)
• Cell Line
• Disease Models, Animal
• Humans
• Hydrogen Peroxide (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Malondialdehyde (metabolism)
• Myocardial Reperfusion Injury (metabolism, prevention & control)
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (administration & dosage, pharmacology)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor C (administration & dosage, pharmacology)