Gene therapy for myocardial angiogenesis: has it come of age?

Vasculogenesis and angiogenesis are the processes responsible for the development of the circulatory system during embryonic and adult life. Vasculogenesis occurs during embryogenesis while angiogenesis refers to blood vessel formation from any preexisting vasculature. Postnatal angiogenesis resumes during reproduction, wound healing, and ischemia. Excess blood vessel formation may contribute to initiating and maintaining many diseases such as chronic inflammatory disorders, tumor growth, restenosis, and atherosclerosis. In contrast. insufficient blood vessel formation is responsible for tissue ischemia, as in coronary artery disease. An increasing number of patients with advanced coronary artery disease remain symptomatic despite maximal interventional, surgical or medical treatment. Ideally, they would benefit most from additional arterial blood supply to ischemic areas of myocardium. Therapeutic angiogenesis, the ability to induce the growth of new blood vessels, is one of the most intriguing new frontiers in interventional cardiology for this growing patient group. Several approaches are currently undergoing intensive experimental investigations or have already entered early clinical trials involving either local angiogenic peptide administration or the transfection of angiogenic genes. Gene therapy for therapeutic myocardial angiogenesis is the most promising synthesis of two emerging technologies. In the following article, we will review the fundamental pathophysiological concepts of gene-based angiogenic therapy, the technical approaches and delivery systems, and the results of the first clinical trials. We will also discuss the controversies and unresolved issues of this new revascularization therapy.