Abstract 16045: MitoQ, a Mitochondrial Targeted Antioxidant, Decreases Maximal Oxidative Phosphorylation and Worsens LV Function in Heart Failure
Heart failure (HF) increases mitochondrial production of reactive oxygen species (ROS) and decreases the capacity for oxidative phosphorylation. It has been proposed that prevention of mitochondrial ROS release by long term treatment with a mitochondrial targeted antioxidant will prevent progression of cardiac dysfunction and improve mitochondrial oxidative phosphorylation in HF. We assessed the effects of mitoquinone (mitoQ, a mitochondria-targeted antioxidant), in rats with pressure-overload HF induced by transverse aortic constriction (TAC). After 14 weeks of TAC, rats were treated with mitoQ for 8 weeks. After 22 weeks post-surgery there was a 50% increase in left ventricular mass by 50%compared to sham in both untreated and mitoQ groups (n=14-18/group). TAC rats had greatly reduced LV fractional shortening compared to SHAM, which was exacerbated by treatment with mitoQ (Figure). Subsarcolemmal (SSM) and interfibrillar mitochondria (IFM) were isolated. There were no differences in respiratory parameters in IFM among groups. In SSM State 3 respiration was decreased in untreated TAC rats compared to SHAM with palmitoylcarnitine as the substrate, which was further worsened by treatment with mitoQ (Figure). Neither TAC or mitoQ affected respiration with glutamate+malate or succinate. Flow cytometry using a cationic carbocyanine dye revealed that SSM were significantly smaller in untreated TAC rats compared to Sham (621 ± 12 vs. 324 ± 15, P<0.05) and had less internal complexity (106 ± 2 vs. 99 ± 1), but were not further altered by mitoQ treatment. Untreated TAC and mitoQ TAC groups displayed increased membrane fluidity in SSM compared to Sham as assessed by fluorescence polarization, but were not further affected by mitoQ. In conclusion, treatment with a mitochondrial targeted antioxidant provided no benefit, and actually worsened oxidative phosphorylation and LV function in HF.
- © 2012 by American Heart Association, Inc.