title: 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.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.|Department of Dermatology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Xu-guang
authors.initials: XG
authors.lastname: Chen
authors.affiliation: Department of Physiology and Key Lab of Human Embryonic Stem Cell of Hubei Province, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Yan-xia
authors.initials: YX
authors.lastname: Lv
authors.affiliation: Department of Physiology and Key Lab of Human Embryonic Stem Cell of Hubei Province, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Li
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Lin-Yun
authors.initials: LY
authors.lastname: Guo
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Ya-mu
authors.initials: YM
authors.lastname: Pan
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: Yu-wen
authors.initials: YW
authors.lastname: Yan
authors.affiliation: Department of Physiology and Pharmacology, The University of Georgia, Athens, GA, 30602, USA.
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.|Department of Physiology and Key Lab of Human Embryonic Stem Cell of Hubei Province, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China. tangjm416@163.com.|Department of Physiology and Key Lab of Human Embryonic Stem Cell of Hubei Province, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China. tangjm416@163.com.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Tang
authors.affiliation: Center for Medical Research and Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, Hubei, People's Republic of China. wanyu@whu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D042582:Vascular Endothelial Growth Factor C / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D011994:Recombinant Proteins; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase
keywords: Apoptosis; Cardiomyocyte; H2O2; Ischemia–reperfusion; VEGF-C