Angiogenesis in the Treatment of Critical Limb Ischemia

This chapter reviews emerging evidence from the fields of gene and cell-based therapies for the management of patients with critical limb ischemia (CLI). Arteriogenesis, also called collateral growth, is the increase in the caliber of pre-existing collateral arterioles capable of compensating for the loss of function of occluded arteries. Vascular endothelial growth factor was one of the early growth factors to be investigated to induce angiogenesis in ischemic tissues. Hypoxia inducible factor-1 (HIF-1) is a recently investigated target for gene therapy in CLI. More than just an endothelial growth factor, it is a transcriptional activator and serves as a master regulator of oxygen homeostasis. A logical direction for future research may be to combine growth factor and cell-based therapy; intramuscular gene therapy could be administered in the ischemic tissue as pretreatment of the target tissue to augment homing of implanted stem cells.