Angiogenesis is a promising novel therapeutic strategy to provide new venue
s for blood flow in patients with severe ischemic heart and peripheral vasc
ular disease, who are not candidates for standard revascularization strateg
ies. We describe the underlying mechanisms involved in physiologic and ther
apeutic angiogenesis, underscoring the relative importance of vasculogenesi
s, angiogenesis, and arteriogenesis. We then present the various gene trans
fer vectors including plasmid, viral, and cell-based vectors, and various d
elivery modalities. The available preclinical data are presented, followed
by a description of preliminary clinical experience, with an emphasis on th
e preliminary nature of these results, which address safety and not efficac
y. Finally, we discuss the promises and pitfalls of clinical angiogenesis a
nd gene transfer studies, stressing the importance of proper design of clin
ical trials and adequate protection of research subjects.