Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation


Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can be associated with the development of the substrate that promotes atrial fibrillation (AF) and its progression. The link, however, between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were well matched for presence of major comorbidities. The overall functional activity of the electron transport chain, NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared to non-AF patients. This was predominantly due to a selective reduction in complex I activity in AF compared to non-AF (0.10±0.01 vs. 0.13±0.01 nmol/min/citrate synthase activity, p=0.03). In addition, the AF patients had a higher level of 4-hydroxynonenal (4-HNE) (77.64±30.2 vs 9.83±2.83 ng/mg protein, p=0.05), a marker of oxidative stress. Our findings suggest that functional activity of complex I is selectively downregulated in patients with AF and could contribute to oxidative stress and the progression of the substrate for AF.

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