Reactive oxygen species and angiotensin II signaling in vascular cells -- implications in cardiovascular disease.
Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II) appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS). ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration ([Ca2+]i), a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.
Multidisciplinary Research Group on Hypertension, Canadian Institute of Health Research, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada. touyzr@ircm.qc.ca
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D000804:Angiotensin II / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology
D017382:Reactive Oxygen Species; D000804:Angiotensin II