We at the Adult Cardiac Catheterization Laboratories and Cardiology Division at UCSF are involved with an exciting new protocol using growth factor therapy in hopes of inducing angiogenesis in patients with chronic angina.

Angiogenesis is the formation of new capillary blood vessels, called collateral vessels, which form from pre-existing blood vessels. When sufficient in size and quantity, collateral vessels may provide perfusion to ischemic territories and actually "bypass" obstructed arteries. Growth factors are protein agents and have been well known to trigger growth responses. Several growth factors have been demonstrated to induce collateral vessel development.

There are two growth factor programs currently under Phase II trial: recombinant Vascular Endothelial Growth Factor (rVEGF, Genentech) and recombinant Fibroblast Growth Factor (rFGF-2, Chiron). Basic fibroblast growth factor (rFGF-2) is just one member of the fibroblast growth factor family, a group of heparin-binding proteins well known as potent mitogens of normal and malignant cells of mesenchymal, neural, and epithelial origin. rFGF-2, like other fibroblast growth factors, is stored primarily in the endothelial basement membrane and is well recognized to promote angiogenesis by acting as an endothelial cell mitogen. The stimuli for the synthesis and secretion of fibroblast growth factors is not well understood although cellular injury, as occurs in myocardial ischemic or infarction, is thought to be one such stimulus. Indeed, a recent study examining the protein content of the pericardial sac of cardiovascular disease patients has demonstrated that rFGF-2 is present at approximately 7 times greater concentration in the pericardial fluid of patients with ischemic heart disease than in the pericardial fluid of patients with non-ischemic heart disease (Fujita et. al., Circulation, 1996).

Subjects being considered for rFGF-2 for myocardial revascularization must have evidence of persistent ischemia despite treatment with optimal medical management and not be candidates for approved myocardial revascularization procedures. Subjects may not be eligible for approved myocardial revascularization procedures because of coronary anatomy, lack of peripheral vessels to harvest and/or poor surgical risk. The hypothesized effect of rFGF-2, revascularization of the myocardium, may constitute a novel form of therapy that would be available to these subjects. To enter the study, a thorough examination or retinal vasculature, renal function and cancer risk must be undertaken.