Reactive oxygen species and angiotensin II signaling in vascular cells: implications in cardiovascular disease

Abstract

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 Ca 2+ concentration ([Ca 2+ ] 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.

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

“…Oxidation-induced impairment of NO also results in reduced opposition to the vasoconstrictive and hypertensive effects of angiotensin II. Angiotensin II decreases NO bioavailability by promoting oxidative stress [172].…”

Cytochrome P450 1B1 Contributes to the Development of Angiotensin II–Induced Aortic Aneurysm in Male Apoe−/− Mice

“…Reactive oxygen species (ROS) produced by inflammatory cells and cells of the vasculature increase activity of one or more signaling molecules, including MMP, and cause lipid peroxidation and tissue damage. 7,8 ROSs are believed to be the major component of the mechanisms that contribute to AAA. 7,8 The metabolism of fatty acids by cyclooxygenase (COX), lipoxygenase, and cytochrome P450 (CYP) enzymes results in the generation of ROS, 8,9 and ROS generated via the activation of NADPH oxidase appears to play a major role in the development of AAA.…”

“…7,8 ROSs are believed to be the major component of the mechanisms that contribute to AAA. 7,8 The metabolism of fatty acids by cyclooxygenase (COX), lipoxygenase, and cytochrome P450 (CYP) enzymes results in the generation of ROS, 8,9 and ROS generated via the activation of NADPH oxidase appears to play a major role in the development of AAA. 10 Previously, we have shown that Ang IIeinduced vascular smooth muscle cell (VSMC) migration, proliferation and hypertrophy, 11 and hypertension 12 depend on CYP1B1, 11,12 a heme-thiolate monooxygenase that is expressed in extrahepatic tissues, including those in the cardiovascular system, 13 and is involved in activating NADPH oxidase and generating ROS.…”

Increased Aortic NADPH Oxidase Activity in Rats With Genetically High Angiotensin-Converting Enzyme Levels

“…Under pathological conditions, ROS contribute to vascular dysfunction and remodeling through oxidative damage. 32 Ang II-stimulated endothelial NADPH oxidase activity is regulated through phosphorylation of p47/phox. 33 After administration of Ang II to rats for 7 days, the activity and the expression of NADPH oxidase was increased by a protein kinase C-dependent mechanism.…”