Gene therapy for ischemic heart disease.
Current pharmacologic therapy for ischemic heart disease suffers multiple limitations such as compliance issues and side effects of medications. Revascularization procedures often end with need for repeat procedures. Patients remain symptomatic despite maximal medical therapy. Gene therapy offers an attractive alternative to current pharmacologic therapies and may be beneficial in refractory disease. Gene therapy with isoforms of growth factors such as VEGF, FGF and HGF induces angiogenesis, decreases apoptosis and leads to protection in the ischemic heart. Stem cell therapy augmented with gene therapy used for myogenesis has proven to be beneficial in numerous animal models of myocardial ischemia. Gene therapy coding for antioxidants, eNOS, HSP, mitogen-activated protein kinase and numerous other anti apoptotic proteins have demonstrated significant cardioprotection in animal models. Clinical trials have demonstrated safety in humans apart from symptomatic and objective improvements in cardiac function. Current research efforts are aimed at refining various gene transfection techniques and regulation of gene expression in vivo in the heart and circulation to improve clinical outcomes in patients that suffer from ischemic heart disease. In this review article we will attempt to summarize the current state of both preclinical and clinical studies of gene therapy to combat myocardial ischemic disease. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy".
Lavu
Madhav
M
Department of Surgery, Division of Cardiothoracic Surgery and the Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, GA 30308, USA.
Gundewar
Susheel
S
Lefer
David J
DJ
D002986:Clinical Trials as Topic; D005346:Fibroblast Growth Factors / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006801:Humans; D017202:Myocardial Ischemia / Q000235:genetics / Q000628:therapy*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D052250:Nitric Oxide Synthase Type III