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

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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.

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Acknowledgments

This study was supported by grants from the National natural Science Foundation of China (81170095 to J.M.T, 81328002 to S.Y.C), Hubei Department Science (2014CFB644 to J.M.T), Hubei Education Department Science Foundation (T201112 to J.M.T), and the National Institutes of Health (HL123302, HL119053, and HL107526 to S.Y.C.).

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Authors and Affiliations

  1. Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Xu-guang Chen, Lei Zhang, Fei Zheng, Jian-Ye Yang, Xiao-lin Li, Lu Wang, Lin-Yun Guo, Ya-mu Pan, Yu-wen Yan, Jia-Ning Wang & Jun-Ming Tang

  2. 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

    Yan-xia Lv, Dan Zhao, Jia-Ning Wang & Jun-Ming Tang

  3. Department of Dermatology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, People’s Republic of China

    Xu-guang Chen

  4. Center for Medical Research and Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, Hubei, People’s Republic of China

    Yu Wan

  5. Department of Physiology and Pharmacology, The University of Georgia, Athens, GA, 30602, USA

    Shi-You Chen

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  1. Xu-guang Chen
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  2. Yan-xia Lv
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  3. Dan Zhao
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Corresponding authors

Correspondence to Jun-Ming Tang or Yu Wan.

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Xu-guang Chen and Yan-xia Lv are co-first authors.

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Chen, Xg., Lv, Yx., Zhao, D. et al. Vascular endothelial growth factor-C protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis. Mol Cell Biochem 413, 9–23 (2016). https://doi.org/10.1007/s11010-015-2622-9

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  • DOI: https://doi.org/10.1007/s11010-015-2622-9

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