Therapeutic angiogenesis for ischemic cardiovascular disease.
In animal models of ischemia, a large body of evidence indicates that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. While many cytokines have angiogenic activity, the best studied both in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown large increases in exercise time and marked reductions in symptoms of angina, as well as objective evidence of improved perfusion and left ventricular function. Larger scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein, and have not yet shown significant improvement in either exercise time or angina when compared to placebo. Larger scale placebo-controlled studies of gene transfer are in progress. Future clinical studies will be required to determine the optimal dose, formulation, route of administration and combinations of growth factors, as well as the requirement for endothelial progenitor cell or stem cell supplementation, to provide effective and safe therapeutic myocardial angiogenesis.
Freedman
S B
SB
Divisions of Cardiology and Vascular Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA.
Isner
J M
JM
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000628:therapy; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000628:therapy; D003327:Coronary Disease / Q000188:drug therapy / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000627:therapeutic use*; D005544:Forecasting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D000860:Hypoxia; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000628:therapy*; D018919:Neovascularization, Physiologic; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor