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

被引:30
|
作者
Chen, Xu-guang [1 ,2 ,5 ]
Lv, Yan-xia [3 ,4 ]
Zhao, Dan [3 ,4 ]
Zhang, Lei [1 ,2 ]
Zheng, Fei [1 ,2 ]
Yang, Jian-Ye [1 ,2 ]
Li, Xiao-lin [1 ,2 ]
Wang, Lu [1 ,2 ]
Guo, Lin-Yun [1 ,2 ]
Pan, Ya-mu [1 ,2 ]
Yan, Yu-wen [1 ,2 ]
Chen, Shi-You [8 ]
Wang, Jia-Ning [1 ,2 ,3 ,4 ]
Tang, Jun-Ming [1 ,2 ,3 ,4 ]
Wan, Yu [6 ,7 ]
机构
[1] Hubei Univ Med, Inst Clin Med, Renmin Hosp, Shiyan 442000, Hubei, Peoples R China
[2] Hubei Univ Med, Dept Cardiol, Renmin Hosp, Shiyan 442000, Hubei, Peoples R China
[3] Hubei Univ Med, Dept Physiol, Shiyan 442000, Hubei, Peoples R China
[4] Hubei Univ Med, Key Lab Human Embryon Stem Cell Hubei Prov, Shiyan 442000, Hubei, Peoples R China
[5] Hubei Univ Med, Renmin Hosp, Dept Dermatol, Shiyan 442000, Hubei, Peoples R China
[6] Wuhan Univ, Sch Basic Med Sci, Med Res Ctr, Wuhan 430071, Hubei, Peoples R China
[7] Wuhan Univ, Sch Basic Med Sci, Dept Physiol, Wuhan 430071, Hubei, Peoples R China
[8] Univ Georgia, Dept Physiol & Pharmacol, Athens, GA 30602 USA
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
Ischemia-reperfusion; Cardiomyocyte; VEGF-C; Apoptosis; H2O2; ISCHEMIA-REPERFUSION INJURY; OXIDATIVE STRESS; PATHWAY; SURVIVAL; ACTIVATION; CELLS; VEGF; TRANSDUCTION; EXPRESSION; RAPAMYCIN;
D O I
10.1007/s11010-015-2622-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 A mu g/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.
引用
收藏
页码:9 / 23
页数:15
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