Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B.
The objective was to examine the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (IR) injury and whether the mechanism was related to vascular endothelial growth factor B (VEGF-B) signaling pathway. Rat hearts were isolated for Langendorff perfusion test and H9c2 cells were used for in vitro assessments. RSV treatment significantly improved left ventricular function, inhibited CK-MB release, and reduced infarct size in comparison with IR group ex vivo. RSV treatment markedly decreased cell death and apoptosis of H9c2 cells during IR. We found that RSV was responsible for the up-regulation of VEGF-B mRNA and protein level, which caused the activation of Akt and the inhibition of GSK3β. Additionally, RSV prevented the generation of reactive oxygen species (ROS) by up-regulating the expression of MnSOD either in vitro or ex vivo. We also found that the inhibition of VEGF-B abolished the cardioprotective effect of RSV, increased apoptosis, and led to the down-regulation of phosphorylated Akt, GSK3β, and MnSOD in H9c2 cells. These results demonstrated that RSV was able to attenuate myocardial IR injury via promotion of VEGF-B/antioxidant signaling pathway. Therefore, the up-regulation of VEGF-B can be a promising modality for clinical myocardial IR injury therapy.
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China; Tianjin Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital, Tianjin 300100, China.
Lei
L
Yang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Yan
Y
Zhang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Mengmeng
M
Zhu
Department of Microbiology, School of Laboratory Medicine, Tianjin Medical University, Tianjin 300203, China.
Qiong
Q
Zhang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Xiaoling
X
Wang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Yanjiao
Y
Wang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Jincai
J
Zhang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Jing
J
Li
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Liang
L
Yang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Jie
J
Liu
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Fei
F
Liu
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Yinan
Y
Yang
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China.
Licheng
L
Kang
Department of Microbiology, School of Laboratory Medicine, Tianjin Medical University, Tianjin 300203, China. Electronic address: shenyanna@sina.com.
Yanna
Y
Shen
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, China. Electronic address: qizhi@nankai.edu.cn.
Zhi
Z
Qi
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D052279:Creatine Kinase, MB Form / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D002316:Cardiotonic Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013267:Stilbenes; D042561:Vascular Endothelial Growth Factor B; D013482:Superoxide Dismutase; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D052279:Creatine Kinase, MB Form; D000077185:Resveratrol
Apoptosis; Myocardial ischemia reperfusion injury; ROS; Resveratrol; VEGF-B