Dai 2011 Circ Res
| Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-CintrΓ³n M, Chen T, Marcinek DJ, Dorn GW 2nd, Kang YJ, Prolla TA, Santana LF, Rabinovitch PS (2011) Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Circ Res 108:837-46. |
Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintron M, Chen T, Marcinek DJ, Dorn GW, Kang YJ, Prolla TA, Santana LF, Rabinovitch PS (2011) Circ Res
Abstract: RATIONALE: Mitochondrial dysfunction has been implicated in several cardiovascular diseases; however, the roles of mitochondrial oxidative stress and DNA damage in hypertensive cardiomyopathy are not well understood.
OBJECTIVE: We evaluated the contribution of mitochondrial reactive oxygen species (ROS) to cardiac hypertrophy and failure by using genetic mouse models overexpressing catalase targeted to mitochondria and to peroxisomes.
METHODS AND RESULTS: Angiotensin II increases mitochondrial ROS in cardiomyocytes, concomitant with increased mitochondrial protein carbonyls, mitochondrial DNA deletions, increased autophagy and signaling for mitochondrial biogenesis in hearts of angiotensin II-treated mice. The causal role of mitochondrial ROS in angiotensin II-induced cardiomyopathy is shown by the observation that mice that overexpress catalase targeted to mitochondria, but not mice that overexpress wild-type peroxisomal catalase, are resistant to cardiac hypertrophy, fibrosis and mitochondrial damage induced by angiotensin II, as well as heart failure induced by overexpression of GΞ±q. Furthermore, primary damage to mitochondrial DNA, induced by zidovudine administration or homozygous mutation of mitochondrial polymerase Ξ³, is also shown to contribute directly to the development of cardiac hypertrophy, fibrosis and failure.
CONCLUSIONS: These data indicate the critical role of mitochondrial ROS in cardiac hypertrophy and failure and support the potential use of mitochondrial-targeted antioxidants for prevention and treatment of hypertensive cardiomyopathy. β’ Keywords: Mitochondria, Reactive oxygen species, Angiotensin, Cardiomyopathy, Heart failure
β’ O2k-Network Lab: US WA Seattle Marcinek DJ
Labels:
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Heart Preparation: Permeabilized tissue
HRR: Oxygraph-2k
