A balancing act: therapeutic approaches for the modulation of angiogenesis.

Therapeutic stimulation of blood vessel growth (angiogenesis) and vessel enlargement (arteriogenesis) has potential in the treatment of ischemic heart and limb diseases. Numerous experiments have been performed involving the delivery of angiogenic factors, or the genes that encode them, to animal disease models, with generally positive results. Although the results of controlled clinical trials have frequently not lived up to expectations, some have demonstrated limited, but significant, improvements. This review covers the transition of therapeutic angiogenesis approaches from preclinical to clinical studies, describes potential problems in the interpretation of the clinical data, and discusses alternative strategies for the treatment of ischemic diseases using endogenous regulation or delivery of progenitor cells.