Therapeutic angiogenesis in the heart: protect and serve.

Therapeutic angiogenesis of coronary and peripheral disease has gone through a period of great hype but has now entered a rational phase. Initial clinical trials with fibroblast growth factor-2 and vascular endothelial growth factor-A have been disappointing, probably owing to suboptimal delivery and incorrect targeting. It is now understood that sustained delivery will be required and that enhancement of collateral formation, rather than angiogenesis, should be targeted. The timing of growth factor therapy might be important as most of these agents protect against ischemic and reperfusion injury, and some may favorably affect post-infarct cardiac remodeling. Preclinical testing of novel delivery strategies, combination therapy as well as novel growth factors and transcription factors pave the way for duly designed and timed clinical trials.