Critical limb ischemia classification and therapeutic angiogenesis

Peripheral vascular disease (PVD) is an independent predictor of increased risk of cardiovascular death. There had been several definitions produced for critical limb ischemia (CLI), the advanced stage of PVD, but they do not correlate well with the eventual outcome. Approximately 20%–30% of patients with CLI cannot be treated by conventional techniques and still require amputation. The aim of therapeutic angiogenesis in PVD and CLI is to improve peripheral extremity perfusion and function within ischemic regions that are not amenable to traditional modes of revascularization. Experimental models of therapeutic angiogenesis using growth factors have produced promising results but results from clinical studies are still not encouraging. Furthermore, with the growth factors being investigated as potential therapeutic agents, there has been no data to suggest which growth factor is the most effective therapeutic agent and the ideal route of administration is still undetermined. In addition, a combination of growth factors may be needed to provide the most effective treatment in view of the complex process of angiogenesis which involves a cascade of events. This review aims to summarize our current understanding of clinical CLI classifications and the potential growth factors for their use in therapeutic angiogenesis.