Angiotensin II-Induced Production of Mitochondrial Reactive Oxygen Species: Potential Mechanisms and Relevance for Cardiovascular Disease
Top Cited Papers
- 1 October 2013
- journal article
- review article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 19 (10), 1085-1094
- https://doi.org/10.1089/ars.2012.4604
Abstract
The role of reactive oxygen species (ROS) in angiotensin II (AngII) induced endothelial dysfunction, cardiovascular and renal remodeling, inflammation, and fibrosis has been well documented. The molecular mechanisms of AngII pathophysiological activity involve the stimulation of NADPH oxidases, which produce superoxide and hydrogen peroxide. AngII also increases the production of mitochondrial ROS, while the inhibition of AngII improves mitochondrial function; however, the specific molecular mechanisms of the stimulation of mitochondrial ROS is not clear. Interestingly, the overexpression of mitochondrial thioredoxin 2 or mitochondrial superoxide dismutase attenuates AngII-induced hypertension, which demonstrates the importance of mitochondrial ROS in AngII-mediated cardiovascular diseases. Although mitochondrial ROS plays an important role in normal physiological cell signaling, AngII, high glucose, high fat, or hypoxia may cause the overproduction of mitochondrial ROS, leading to the feed-forward redox stimulation of NADPH oxidases. This vicious cycle may contribute to the development of pathological conditions and facilitate organ damage in hypertension, atherosclerosis, and diabetes. The development of antioxidant strategies specifically targeting mitochondria could be therapeutically beneficial in these disease conditions.Keywords
This publication has 69 references indexed in Scilit:
- Cross talk between mitochondria and NADPH oxidasesFree Radical Biology & Medicine, 2011
- Redox regulation of the mitochondrial KATP channel in cardioprotectionBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2011
- Nox4 regulates Nrf2 and glutathione redox in cardiomyocytes in vivoFree Radical Biology & Medicine, 2011
- Angiotensin II and angiotensin-1-7 redox signaling in the central nervous systemCurrent Opinion in Pharmacology, 2011
- NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesisProceedings of the National Academy of Sciences of the United States of America, 2010
- NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heartProceedings of the National Academy of Sciences of the United States of America, 2010
- Subcellular localization of Nox4 and regulation in diabetesProceedings of the National Academy of Sciences of the United States of America, 2009
- Renin-angiotensin-aldosterone system-mediated redox effects in chronic kidney diseaseTranslational Research, 2009
- Calcium-Dependent NOX5 Nicotinamide Adenine Dinucleotide Phosphate Oxidase Contributes to Vascular Oxidative Stress in Human Coronary Artery DiseaseJournal of the American College of Cardiology, 2008
- Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide productionFree Radical Biology & Medicine, 2008