Angiogenesis of the heart.
Despite continued advances in the prevention and treatment of coronary artery disease, there are still a large number of patients who are not candidates for the conventional revascularization techniques of balloon angioplasty and stenting, or coronary artery bypass grafting (CABG). Therapeutic angiogenesis, in the form of the administration of growth factor protein or gene therapy, has emerged as a promising new method of treatment for patients with coronary artery disease. The goal of this strategy is to promote the development of supplemental blood conduits that will act as endogenous bypass vessels. New vessel formation occurs through the processes of angiogenesis, vasculogenesis, and arteriogenesis, under the control of growth factors such as those that belong to the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and angiopoeitin (Ang) families of molecules. Preclinical studies have suggested that such an approach is both feasible and effective; however many questions remain to be answered. This review will address the elements of pharmacologic revascularization, focusing on gene and protein-based therapy. The important growth factors, the vector (for gene therapy), routes of delivery, the desired therapeutic effect, and quantifiable clinical end points for trials of angiogenesis will all be addressed.
Kutryk
Michael J B
MJ
Division of Cardiology, Terrence Donnelly Heart Center, St. Michael's Hospital, University of Toronto, Toronto M5B 1W8, Ontario, Canada. kutrykm@smh.toronto.on.ca
Stewart
Duncan J
DJ
D000818:Animals; D002986:Clinical Trials as Topic; D003331:Coronary Vessels / Q000254:growth & development*; D016228:Endothelial Growth Factors / Q000009:adverse effects / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009204:Myocardial Revascularization / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012107:Research Design
D016228:Endothelial Growth Factors