Monotherapy versus combination therapy of angiogenic and arteriogenic factors for the treatment of ischemic disorders.

The idea of delivery of proangiogenic factors to the ischemic region of myocardium or skeletal muscles was proposed more than 30 years ago and abundant preclinical data validate this concept. However, clinical experience with this approach has generally produced unfulfilled promises. Although reestablishment of functional collateral networks for improvement of blood perfusion in ischemic tissues is an undisputed concept for therapeutic intervention, the molecular mechanism underlying collaterogenesis under tissue hypoxia remains poorly understood. Critical issues including the therapeutic efficacy of monotherapy vs. combination with arteriogenic therapy, drug release, optimal dose, and time scale of delivery remain to be resolved. The aim of this review is to discuss molecular mechanisms of angiogenesis and arteriogenesis, to better design clinical trials, and to improve therapeutic efficacy of proangiogenic and arteriogenic factors for the treatment of ischemic diseases.