Several polypeptides with the ability to induce blood vessel development (angiogenesis) have been identified during the last decade, agents that may have the potential to facilitate myocardial revascularization in patients with coronary heart disease. We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF), a pluripotent mitogen of mesodermally-derived cells, and vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and vascular permeability factor, enhance coronary collateral development in dogs when administered for r4 weeks. The benefits of these growth factors must be weighed against potential untoward effects of long term administration. In particular, bFGF could potentially exacerbate neointimal smooth muscle cell (SMC) hyperplasia, a fundamental component of atherosclerosis, and VEGF could have deleterious effects related to vascular hyperpermeability. This investigation has two aims: 1) to ascertain whether only 7 days of bFGF or VEGF treatment would improve myocardial collateral perfusion; 2) to determine whether these peptides induce neointimal SMC hyperplasia. Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery. Ten days after ameroid placement, dogs underwent balloon denudation injury of the ilio-femoral artery and were randomized to receive bFGF 1.74 mg (n=9), VEGF 0.72 mg (n=9), or saline (n=10) as a daily left atrial bolus for 7 days. Administration of bFGF was associated with a 68% increase in coronary collateral blood flow at the end of treatment, with a 46% increase persisting 3 weeks after cessation of treatment. Basic FGF did not exacerbate neointimal SMC accumulation after vascular injury. VEGF had no apparent effect on collateral flow, but exacerbated neointimal SMC proliferation following vascular injury. These data demonstrate that short term bFGF treatment enhances collateral development, and the beneficial effects on collateral development can be dissociated from potential deleterious responses to vascular injury.
