Angiotensin II-induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease

SI Dikalov, RR Nazarewicz - Antioxidants & redox signaling, 2013 - liebertpub.com
SI Dikalov, RR Nazarewicz
Antioxidants & redox signaling, 2013liebertpub.com
Significance: 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 …
Abstract
Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: The development of antioxidant strategies specifically targeting mitochondria could be therapeutically beneficial in these disease conditions. Antioxid. Redox Signal. 19, 1085–1094.
Mary Ann Liebert