Activation of NADPH oxidase mediates mitochondrial oxidative stress and atrial remodeling in diabetic rabbits.

AIMS

The mechanisms of atrial fibrillation (AF) in diabetes mellitus (DM) involve a complex interplay between increased oxidative stress, mitochondrial dysfunction and atrial remodeling. In this study, we examined the effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation on mitochondrial oxidative stress and atrial remodeling in a rabbit model of diabetes mellitus (DM).

MAIN METHODS

Healthy rabbits were selected and randomly divided into control, diabetic and apocynin administration group. Parameters of echocardiography, atrial electrophysiology, oxidative stress and mitochondrial function were compared between the different groups.

KEY FINDINGS

Compared to the control group, the DM group showed higher activity of NADPH oxidase, increased oxidative stress, larger left atrial diameter, a reduction in atrial mean conduction velocity. These findings were associated with increased interstitial fibrosis of the atria and higher atrial fibrillation (AF) inducibility. Moreover, atrial ultrastructure and mitochondrial function such as the mitochondrial respiratory control rate (RCR) were impaired. NADPH oxidase inhibition using the pharmacological agent apocynin improved these changes.

SIGNIFICANCE

NADPH oxidase activity plays an important role in mitochondrial oxidative stress, which is associated with AF inducibility by promoting adverse atrial remodeling. The NADPH oxidase inhibitor apocynin can prevent these pathological changes and may be a potential drug for AF treatment.