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

被引:0
|
作者
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
机构
[1] Hubei University of Medicine,Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital
[2] Hubei University of Medicine,Department of Physiology and Key Lab of Human Embryonic Stem Cell of Hubei Province
[3] Hubei University of Medicine,Department of Dermatology, Renmin Hospital
[4] Wuhan University,Center for Medical Research and Department of Physiology, School of Basic Medical Sciences
[5] The University of Georgia,Department of Physiology and Pharmacology
来源
关键词
Ischemia–reperfusion; Cardiomyocyte; VEGF-C; Apoptosis; H; O;
D O I
暂无
中图分类号
学科分类号
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 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.
引用
收藏
页码:9 / 23
页数:14
相关论文
共 50 条
  • [1] Vascular endothelial growth factor-C protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis
    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
    [J]. MOLECULAR AND CELLULAR BIOCHEMISTRY, 2016, 413 (1-2) : 9 - 23
  • [2] Depletion of PHD3 protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis
    Xie, Liang
    Pi, Xinchun
    Wang, Zhongjing
    He, Jun
    Willis, Monte S.
    Patterson, Cam
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2015, 80 : 156 - 165
  • [3] iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis
    Yagudin, Timur
    Zhao, Yue
    Gao, Haiyu
    Zhang, Yang
    Yang, Ying
    Zhang, Xiaofang
    Ma, Wenbo
    Daba, Tolessa Muleta
    Ishmetov, Vladimir
    Kang, Kai
    Yang, Baofeng
    Pan, Zhenwei
    [J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2021, 53 (01) : 102 - 111
  • [4] Ethanol protects from injury due to ischemia and reperfusion by increasing vascularity via vascular endothelial growth factor
    Louboutin, Jean-Pierre
    Marusich, Elena
    Gao, Ehre
    Agrawal, Lokesh
    Koch, Walter J.
    Strayer, David S.
    [J]. ALCOHOL, 2012, 46 (05) : 441 - 454
  • [5] Bosentan protects the spinal cord from ischemia reperfusion injury in rats through vascular endothelial growth factor receptors
    S Gong
    Z Seng
    W Wang
    J Lv
    Q Dong
    B Yan
    L Peng
    X He
    [J]. Spinal Cord, 2015, 53 : 19 - 23
  • [6] Bosentan protects the spinal cord from ischemia reperfusion injury in rats through vascular endothelial growth factor receptors
    Gong, S.
    Seng, Z.
    Wang, W.
    Lv, J.
    Dong, Q.
    Yan, B.
    Peng, L.
    He, X.
    [J]. SPINAL CORD, 2015, 53 (01) : 19 - 23
  • [7] Quantification of vascular endothelial growth factor-C
    Al-Mowallad, AF
    Li, CG
    Wilson, P
    Duff, S
    Costello, B
    Kumar, S
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 2004, 289 (1-2) : 239 - 240
  • [8] Vascular endothelial growth factor-C: A growth factor for lymphatic and blood vascular endothelial cells
    Enholm, B
    Jussila, L
    Karkkainen, M
    Alitalo, K
    [J]. TRENDS IN CARDIOVASCULAR MEDICINE, 1998, 8 (07) : 292 - 297
  • [9] VASCULAR ENDOTHELIAL GROWTH FACTOR PROTECTS THE VASCULAR ENDOTHELIUM FROM APOPTOSIS BY INHIBITING PRO-APOPTOTIC ENDONUCLEASES
    Al-Fakhri, N.
    Mey, L.
    Hoermann, M.
    Kharip, Z.
    Nemeth, K.
    Hildenberg, A.
    Loewer, C.
    Heidt, M.
    Renz, H.
    [J]. CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 2011, 49 : S285 - S285
  • [10] Growth differentiation factor (GDF)-15 protects the heart from ischemia/reperfusion injury in vivo
    Kempf, T
    Willenbockel, C
    Widera, C
    Niessen, HW
    Molkentin, JD
    Wollert, KC
    [J]. CIRCULATION, 2005, 112 (17) : U335 - U335