Fibroblast growth factor-mediated angiogenesis for the treatment of ischemia. Lessons learned from experimental models and early human experience.
Fibroblast growth factors (FGFs) are a family of nearly twenty heparin-binding growth factors. They are widely distributed throughout the body, but their activity is tightly controlled. This review will focus on fibroblast growth factor-1/FGF-1) and fibroblast growth factor-2 (FGF-2) which have been studied extensively in vitro and in vivo. These two growth factors stimulate the proliferation of cells of mesenchymal origin, including the three principal vascular cell types: fibroblasts, endothelial cells and smooth muscle cells. The molecular characteristics of these growth factors, their receptors, distribution, function, pharmacokinetics, hemodynamic effects and toxicity are reviewed herein. The experimental evidence for the potential for FGFs as therapeutic agents for the treatment of progressive myocardial ischemia, acute myocardial ischemia, and peripheral limb ischemia is also analyzed. It is not known to what extent the results of animal studies can be extrapolated to humans with ischemic cardiovascular disease. Clinical trials have been initiated, and there is a growing hope that the pharmacologic use of growth factors will represent a viable therapeutic alternative for patients with ischemic cardiovascular disease.
Gonçalves
L M
LM
Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1518, USA. goncalvl@gwgate.nhlbi.nih.gov
D000818:Animals; D004195:Disease Models, Animal; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D005121:Extremities / Q000098:blood supply*; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*
D005346:Fibroblast Growth Factors