Impact Of Mitochondria Phospholipid Hydroperoxide Glutathione Peroxidase (Mphgpx) Overexpression On The Type 1 Diabetic Heart

Mitochondrial dysfunction is a major contributor to diabetic cardiomyopathy during type 1 diabetes mellitus (DM). In type 1 DM, interfibrillar mitochondria (IFM) display changes in reactive oxygen species production and oxidative damage. The goal of this study was to determine whether overexpression of mitochondria phospholipid hydroperoxide glutathione peroxidase (mPHGPx), an antioxidant enzyme, could attenuate cardiac and mitochondrial function associated with type 1 DM. MPHGPx transgenic mice and littermate controls were made diabetic and five weeks post diabetic onset, cardiac contractile function was measured. Ejection fraction, fractional shortening and cardiac output were significantly decreased in diabetic versus control hearts ( P <0.05 for all three), with mPHGPx overexpression restoring function to control levels ( p <0.05). Mitochondrial respiration rates (state 3 and 4) were significantly decreased in diabetic IFM versus control ( p <0.05) and were restored with mPHGPx overexpression. Reactive oxygen species and oxidative stress levels were higher in diabetic IFM compared to control ( p <0.05), which were attenuated with mPHGPx overexpression ( p <0.05). In summary, overexpression of mPHGPx restored cardiac and mitochondrial function normally lost during a type 1 DM insult by preserving IFM function. ( Support: NIH DP2DK083095, NIH T32HL090610, AHA 10PRE3420006, NIH S10 RR‐026378 )