Details

Autor(en) / Beteiligte

• Chen, Xu-guang
• Lv, Yan-xia
• Zhao, Dan
• Zhang, Lei
• Zheng, Fei
• Yang, Jian-Ye
• Li, Xiao-lin
• Wang, Lu
• Guo, Lin-Yun
• Pan, Ya-mu
• Yan, Yu-wen
• Chen, Shi-You
• Wang, Jia-Ning
• Tang, Jun-Ming
• Wan, Yu

Titel

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

Ist Teil von

• Molecular and cellular biochemistry, 2016-02, Vol.413 (1-2), p.9-23

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 H 2 O 2 -induced H9c2 cardiomyocytes, which mimicked the I/R injury in vivo, VEGF-C pre-treatment decreased the LDH release and MDA content, blocked H 2 O 2 -induced apoptosis by inhibiting the pro-apoptotic protein Bax expression and its translocation to the mitochondrial membrane, and consequently attenuated H 2 O 2 -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 H 2 O 2 -induced activation of intrinsic apoptotic pathway. VEGF-C exerts its cardiac protection following I/R injury via its anti-apoptotic effect.