The Anti-inflammatory and Proangiogenic Properties of High-Density Lipoproteins: An Emerging Role in Diabetic Wound Healing.

Significance: Prolonged inflammation and impaired angiogenesis are the two principal factors that prevent successful wound healing, which is exacerbated in people with diabetes. There is a significant need for new wound healing treatments that target both these factors simultaneously. This review discusses the emerging evidence that high-density lipoproteins (HDL) have pleiotropic wound healing benefits. Recent Advances: Numerous in vitro and in vivo studies have demonstrated the anti-inflammatory and proangiogenic effects of HDL. In endothelial cells, HDL mediate these effects through interaction with the scavenger receptor SR-BI, which activates the PI3K/Akt pathway, causing a decrease in inflammatory protein production and an increase in proangiogenic growth factors. In macrophages, HDL inhibit inflammation through suppression of the nuclear factor kappa B activation pathway. This review details the molecular disturbances that cause impaired wound healing in diabetes with a particular focus on inflammation and angiogenesis and the pathways in which HDL provide benefit. Critical Issues: Diabetic foot ulcers (DFUs) impose a major public health challenge worldwide. It is estimated that 20% patients with DFUs require amputation, which is accompanied by a significant social and economic burden. To date, there are no therapeutic agents with pleiotropic effects that actively improve wound healing, highlighting a therapeutic void for this complex disease.