Therapeutic angiogenesis: time for the next phase.

Restoring blood flow is the most effective means to limit damage to ischemic tissue. Since the 1960s, surgical placement of bypass grafts for coronary artery disease (CAD) and peripheral vascular disease has effectively and durably restored blood flow to ischemic tissue. Nonsurgical revascularization was introduced clinically starting in the 1970s. Thrombolytic therapy is used to treat acute thrombotic arterial occlusion. Angioplasty combined with stent placement is currently the most frequently applied nonsurgical method of relieving acute coronary ischemia. Now, therapeutic angiogenesis, the promotion of new vessel growth using vascular growth factors, is the latest and perhaps most exciting strategy for revascularizing ischemic tissue (1–4). Angiogenesis is induced by invasive (surgical or catheter-based approaches) and noninvasive (intramuscular or intra-arterial) delivery of a variety of promoters (5). Vascular endothelial growth factor (VEGF) (6) and basic fibroblastic growth factor (bFGF) (7) are the angiogenic agents in most current clinical studies.