Atrial Fibrillation Is Associated With Impaired Atrial Mitochondrial Energetics and Supercomplex Formation in Adults With Type 2 Diabetes.

Abstract

Type 2 diabetes mellitus is a chronic progressive disease that is associated with increased risk for cardiovascular diseases and with impaired mitochondrial metabolism in cardiac and skeletal muscles. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with significant morbidity and mortality. Type 2 diabetes is also one of the prevalent concomitant diseases in patients with AF. During AF, myocardial energy demand is high due to electrical activity. To date, however, very little is known about the effects of AF on atrial muscle mitochondrial energetics. We hypothesized that preexisting fibrillation or type 2 diabetes impacts atrial mitochondrial energetics and electron transport chain supercomplexes. Atrial appendages were collected from patients who had consented and who had and did not have preexisting AF and were undergoing coronary artery bypass graft surgery. Mitochondrial functional analyses were conducted in permeabilized myofibers using high-resolution respirometry. Results show impaired complex I and II function in addition to impaired electron transport chain supercomplex assembly in patients with diabetes and AF compared to patients with diabetes but without AF. There were no differences in mitochondrial content in atrial muscle between the groups. There was a strong trend for increased oxidative damage (protein carbonyls) in patients with diabetes and AF compared to patients with diabetes but without AF. Overall, findings suggest impaired mitochondrial function in AF and type 2 diabetes.