Mitochondrial DNA Damage Linked to Vascular Alterations in Diabetics

Increased mitochondrial DNA damage in peripheral blood mononuclear cells of patients with diabetes mellitus and clinical atherosclerotic cardiovascular disease is associated with microvascular alterations, specifically, microvascular pulsability. The study, “Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease,” was published in the journal Cardiovascular Diabetology.

Diabetes mellitus is an established significant risk factor for cardiovascular disease. However, the underlying mechanisms linking diabetes with defects in vascular function remain incompletely understood. Previous studies showed that mitochondria dysfunction, associated with increased levels of reactive oxygen species, in peripheral blood mononuclear cells (i.e., lymphocytes, monocytes or macrophages, key cells of the immune system) is linked to vascular dysfunction in patients with diabetes.

Researchers investigated the relation between mitochondrial DNA damage in peripheral blood mononuclear cells and vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. They determined vascular function (via a non-invasive method) and mitochondrial DNA damage in a population of patients with atherosclerotic cardiovascular disease alone (n=275), diabetes mellitus alone (n = 74), and combined atherosclerotic cardiovascular disease with diabetes mellitus (n = 48). Findings were compared to those of 98 healthy controls.

The team found that mitochondrial DNA damage in peripheral blood mononuclear cells was higher in all conditions, i.e., clinical atherosclerosis, diabetes mellitus, and both conditions combined, when compared to controls. The levels of mitochondrial DNA damage in patients with diabetes mellitus compared to established atherosclerotic disease were similar.

Additionally, researchers observed that mitochondrial DNA damage was associated with a higher baseline pulse amplitude, denoting alterations to the microvascular pulsatility. But no association was found between mitochondrial DNA damage and vasodilator responses.

In conclusion, the findings support the idea that diabetes mellitus and atherosclerotic cardiovascular disease associate with increased mitochondrial DNA damage, suggesting a link between mitochondrial dysfunction and microvascular dysfunction, specifically microvascular pulsatility but not vasodilator function. Researchers highlighted that future studies should further clarify how mitochondria DNA damage associates with microvascular disease, and if mitochondria-targeted therapies may carry benefits for the cardiovascular system.