Abstract | RATIONALE: OBJECTIVE: 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 Gαq. Furthermore, primary damage to mitochondrial DNA, induced by zidovudine administration or homozygous mutation of mitochondrial polymerase γ, is also shown to contribute directly to the development of cardiac hypertrophy, fibrosis and failure. CONCLUSIONS:
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Authors | Dao-Fu Dai, Simon C Johnson, Jason J Villarin, Michael T Chin, Madeline Nieves-Cintrón, Tony Chen, David J Marcinek, Gerald W Dorn 2nd, Y James Kang, Tomas A Prolla, Luis F Santana, Peter S Rabinovitch |
Journal | Circulation research
(Circ Res)
Vol. 108
Issue 7
Pg. 837-46
(Apr 01 2011)
ISSN: 1524-4571 [Electronic] United States |
PMID | 21311045
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- DNA, Mitochondrial
- Reactive Oxygen Species
- Reverse Transcriptase Inhibitors
- Angiotensin II
- Zidovudine
- Catalase
- GTP-Binding Protein alpha Subunits, Gq-G11
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Topics |
- Angiotensin II
(adverse effects, pharmacology)
- Animals
- Cardiomegaly
(chemically induced, physiopathology)
- Catalase
(genetics, metabolism)
- DNA Damage
(physiology)
- DNA, Mitochondrial
(drug effects)
- GTP-Binding Protein alpha Subunits, Gq-G11
(genetics, metabolism)
- Gene Expression Regulation
(drug effects)
- Heart Failure
(metabolism, physiopathology)
- Mice
- Mice, Transgenic
- Mitochondria, Heart
(physiology)
- Models, Animal
- Myocytes, Cardiac
(metabolism)
- Oxidative Stress
(physiology)
- Reactive Oxygen Species
(metabolism)
- Reverse Transcriptase Inhibitors
(pharmacology)
- Zidovudine
(pharmacology)
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