The number one cause of mortality in the US is cardiovascular related disease. Future predictions do not see a reduction in this rate especially with the continued rise in obesity [1,2]. Even so, potential molecular therapeutic targets for cardiac gene delivery are in no short supply thanks to continuing advances in molecular cardiology. However, efficient and safe delivery remains a bottleneck in clinical gene therapy [3] Keywords myocardium; angiogenesis; non-viral gene delivery; ischemia Viral vectors are looked upon favorably for their high transduction efficiency, although their ability to elicit toxic immune responses remains [4]. However, this high transduction does not necessarily translate into improved efficacy [5]. Naked DNA remains the preferred method of DNA delivery to cardiac myocardium and has been explored extensively in clinical trials. The results from these trials have demonstrated efficacy in regards to secondary end-points of reduced symptomology and perfusion, but have failed to establish significant angiogenesis or an increase in myocardial function [6]. This may be due in part to reduced transfection efficiency but can also be attributed to use of suboptimal candidate genes.Correspondence should be addressed to: David A. Bull, M.D., Division of Cardiothoracic Surgery, Room 3C127, 30 North 1900 East, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, Phone 801-581-5311, FAX 801-585-3936, david.bull@hsc.utah.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. However, little development has been seen in the use of new gene agents for treatment of myocardial ischemia and infarction. Current treatment consists of using mitogenic factors, described decades earlier, alone or in combination to spur angiogenesis or modulating intracellular Ca2+ homeostasis through SERCA2a but have to date, failed to demonstrate clinical efficacy. Recent data suggests that axonal guidance cues also act on vasculature neogenesis and provide a new means of investigation for treatment.
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Clinical Gene Therapy for Therapeutic Myocardial AngiogenesisIschemic heart disease is the leading cause of death in the United States today. Currently, the mainstay of therapy for ischemic heart disease (IHD) is revascularization. Nearly 2,000,000 cardiac catheterizations and 553,000 coronary artery bypass grafting procedures are performed annually [9]. Technological developments in these areas have led to an improved survival and quality of life for patients with IHD. However, increasing evidence suggests that revascularization alone is insuffici...