Original ArticlesGene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart
Section snippets
Acute myocardial infarction model
Twelve Wistar male rats were used for this study. Humane animal care complied with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resource and published by the National Institutes of Health (NIH Publication No. 86-23, revised 1985). Acute myocardial infarction was induced as described elsewhere [11]. Briefly, the rats (8 weeks after birth)
Changes in HGF and c-Met receptor mRNA expression after myocardial infarction
Thirty-six percent of the infarcted rats died within 6 hours after the operation. No technical failure occurred during this study. We first analyzed changes in the expression of HGF and c-Met/HGF receptor mRNAs in the left ventricle of the infarcted heart by using RT-PCR after left coronary artery ligation. Three rats were used at each time point: 24 hours, 3 days, and 7 days after ligation. RT-PCR was performed using specific sets of primers that detect rat HGF and c-Met receptor mRNAs. The
Comment
Myocardial ischemia and subsequent reperfusion induce myocardial cellular injury, including apoptosis and/or necrosis in cardiac myocytes and coronary endothelial cells [17]. Cell death in cardiac myocytes is in turn accompanied by myocardial dysfunction. Prevention of cellular injury and death attenuates the magnitude of myocardial dysfunction. Therefore, application of growth factors that target cardiac myocytes and/or endothelial cells may be potentially beneficial for the prevention of
Acknowledgements
We are grateful to Dr Ryuichi Morishita, Osaka University Medical School, Department of Geriatric Medicine, Suita, Japan, for his technical support. This work was supported by a Grant-in-Aid for Scientific Research in Japan.
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Cardioprotection by gene therapy: A review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology
2015, International Journal of CardiologyNonviral delivery of genetic medicine for therapeutic angiogenesis
2012, Advanced Drug Delivery ReviewsCitation Excerpt :Therapeutic angiogenesis, induced by exogenous administration of genes encoding angiogenic growth factors, has emerged as a potential treatment for patients who cannot be treated with surgical intervention or angioplasty for revascularization [6]. Indeed, gene transfer of angiogenic growth factors including vascular endothelial growth factor (VEGF) [7–10], basic fibroblast growth factor (bFGF) [11], and hepatocyte growth factor (HGF) [12] has resulted in enhanced angiogenesis and functional recovery of ischemic tissues in an animal model of myocardial or hindlimb ischemia. Clinical gene therapy with angiogenic growth factors has also shown therapeutic potential for patients with severe myocardial ischemia or critical limb ischemia [13,14].
Intracoronary mesenchymal stem cells promote postischemic myocardial functional recovery, decrease inflammation, and reduce apoptosis via a signal transducer and activator of transcription 3 mechanism
2011, Journal of the American College of SurgeonsCitation Excerpt :STAT3KO MSCs release more HGF but less IGF-1 than their WT counterparts, a finding with unclear significance. HGF10,25-26 VEGF,8,10and IGF-126,27 are all known to be cardioprotective in the setting of I/R. Considering that VEGF is a critical mediator of MSC-derived cardioprotection8 and the substantial reduction in IGF-1 levels we observed in STAT3KO MSCs, reduced functional recovery in STAT3KO MSC-treated hearts is unsurprising. The moderate increase in HGF production by STAT3KO MSCs would not be expected to compensate for reductions in VEGF and IGF-1.
The Role of Cytoprotective Cytokines in Cardiac Ischemia/Reperfusion Injury
2008, Journal of Surgical ResearchCitation Excerpt :Previous studies have shown that expression of HGF and its receptor c-Met are transiently up-regulated in the myocardium of developing hearts in mice [16], and HGF plasma levels are markedly elevated in patients with acute myocardial infarction [17]. It has also been shown that HGF gene transfection into myocardium reduces ischemia/reperfusion injury [18]. Moreover, Nakamura et al. have recently shown by neutralization of endogenous HGF and intravenous supplementation of recombinant HGF, that endogenous HGF is cardioprotective and exogenous HGF attenuates ischemia/reperfusion injury by directly protecting cardiomyocytes [19].
Angiogenesis
2008, MicrocirculationIn Vivo Hepatocyte Growth Factor Gene Transfer Reduces Myocardial Ischemia-Reperfusion Injury Through Its Multiple Actions
2007, Journal of Cardiac FailureCitation Excerpt :In vitro studies showed that HGF has an antioxidant effect.7,8 Gene transfer of human cDNA HGF has been reported to improve cardiac function in isolated rat hearts.6 Moreover, it has been reported that HGF induces angiogenic and antifibrotic effects in a model of cardiomyopathy and heart failure.9