Mitochondrial regulation of diabetic vascular disease: an emerging opportunity

Abstract

Diabetes-related vascular complication rates remain unacceptably high despite guideline-based medical therapies that are significantly more effective in individuals without diabetes. This critical gap represents an opportunity for researchers and clinicians to collaborate on targeting mechanisms and pathways that specifically contribute to vascular pathology in patients with diabetes mellitus. Dysfunctional mitochondria producing excessive mitochondrial reactive oxygen species (mtROS) play a proximal cell-signaling role in the development of vascular endothelial dysfunction in the setting of diabetes. Targeting the mechanisms of production of mtROS or mtROS themselves represents an attractive method to reduce the prevalence and severity of diabetic vascular disease. This review focuses on the role of mitochondria in the development of diabetic vascular disease and current developments in methods to improve mitochondrial health to improve vascular outcomes in patients with DM.

Keywords: Abbreviations: CuZn SOD; DM; Drp1; ETC; FFA; HUVECs; Mdivi-1; Mfn1/2; MnSOD; NMN; NO; NR; OPA-1; SIRT1; SS; Szeto-Schiller; UCP2; copper-zinc superoxide dismutase; diabetes mellitus; dynamin-related protein 1; electron transport chain; free fatty acids; human umbilical vein endothelial cells; mPTP; manganese superoxide dismutase; mitochondrial division inhibitor 1; mitochondrial membrane potential; mitochondrial permeability transition pore; mitochondrial reactive oxygen species; mitofusin 1/2; mtROS; nicotinamide mononucleotide; nicotinamide riboside; nitric oxide; optic atrophy protein 1; sirtuin-1; uncoupling protein 2; Δψ(m).