The multiple actions of angiotensin II in atherosclerosis.
Angiotensin II (Ang II), the effector peptide of the renin-angiotensin system, has been implied in the pathogenesis of atherosclerosis on various levels. There is abundant experimental evidence that pharmacological antagonism of Ang II formation by angiotensin converting enzyme inhibition or blockade of the cellular effects of Ang II by angiotensin type 1 receptor blockade inhibits formation and progression of atherosclerotic lesions. Angiotensin promotes generation of oxidative stress in the vasculature, which appears to be a key mediator of Ang II-induced endothelial dysfunction, endothelial cell apoptosis, and lipoprotein peroxidation. Ang II also induces cellular adhesion molecules, chemotactic and proinflammatory cytokines, all of which participate in the induction of an inflammatory response in the vessel wall. In addition, Ang II triggers responses in vascular smooth muscle cells that lead to proliferation, migration, and a phenotypic modulation resulting in production of growth factors and extracellular matrix. While all of these effects contribute to neointima formation and development of atherosclerotic lesions, Ang II may also be involved in acute complications of atherosclerosis by promoting plaque rupture and a hyperthrombotic state. Accordingly, Ang II appears to have a central role in the pathophysiology of atherosclerosis.
Schmidt-Ott
K M
KM
Department of Physiology, College of Medicine, Box 100274, University of Florida, 32610, Gainesville, FL, USA.
Kagiyama
S
S
Phillips
M I
MI
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism*; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D017382:Reactive Oxygen Species / Q000502:physiology; D012083:Renin / Q000378:metabolism
D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D012083:Renin