Angiogenesis in Diabetes. Unraveling the Angiogenic Paradox

Angiogenesis can be regarded as a double-edged sword given its useful actions in repairing tissues, and secondly due to its effects in enhancing tissue damage. Angiogenesis is actually involved in the pathogenesis of disorders in which the inflammatory component is a major contributor for disease progression, such as diabetes. It is now stated that angiogenesis together with vasculogenesis partake to neovascular development. A peculiar characteristic of diabetes is the co-existence of vascular impairment and excessive angiogenesis in distinct organs. But despite this knowledge, many questions remain unanswered. Due to the importance of these systems in diabetes-associated complications, a better understanding of the molecular and cellular processes may open new mechanism-based therapeutic options. Accordingly, the available treatment strategies for diabetes management are not completely efficient, as highlighted by the elevated mortality and morbidity rates associated with this condition. Diabetic nephropathy, which may evolve to end-stage renal failure, and diabetic retinopathy that may progress to blindness are important causes of morbidity. Additionally, chronic nonhealing skin ulceration greatly impairs the quality of life of diabetic patients, resulting often in limb amputation. Cardiovascular events, in turn, are responsible for a significant number of deaths in diabetes. This review aims at highlighting the state-of-the-art in diabetic vascular complications, and comprehends the characterization of neovascular system alterations. The elucidation of the diabetic-associated angiogenic paradox is fundamental for prospecting novel therapeutic interventions.