Diabetes and Wound Angiogenesis

Abstract

Diabetes Mellitus Type II (DM2) is a growing international health concern with no end in sight. Complications of DM2 involve a myriad of comorbidities including the serious complications of poor wound healing, chronic ulceration, and resultant limb amputation. In skin wound healing, which has definite, orderly phases, diabetes leads to improper function at all stages. While the etiology of chronic, non-healing diabetic wounds is multi-faceted, the progression to a non-healing phenotype is closely linked to poor vascular networks. This review focuses on diabetic wound healing, paying special attention to the aberrations that have been described in the proliferative, remodeling, and maturation phases of wound angiogenesis. Additionally, this review considers therapeutics that may offer promise to better wound healing outcomes.

Keywords: angiogenesis; diabetes; wound healing.

Figure 1

Events in wound angiogenesis. In the normal quiescent state, capillaries (pink) are surrounded by pericytes (blue). Following injury, the hypoxia that is created by the disruption of the vasculature stimulates the production of pro-angiogenic factors (green triangle), resulting in the sprouting of immature and disorganized new capillaries. In the remodeling phase, anti-angiogenic factors (red triangle) cause most of the newly formed capillaries to undergo apoptosis, and the capillary bed is pruned. Maturation factors (gray triangle) support the recruitment of stabilizing pericytes and the maturation of the basement membrane on the new capillaries. The result is a stable, well perfused capillary bed with a vessel density similar to normal uninjured tissue.