The multiple actions of angiotensin II in atherosclerosis

Angiotensin II (Ang II), the effector peptide of the renin-angiotensin syst em, has been implied in the pathogenesis of atherosclerosis on various leve ls. There is abundant experimental evidence that pharmacological antagonism of Ang II formation by angiotensin converting enzyme inhibition or blockad e of the cellular effects df 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 whic h participate in the induction of an inflammatory response in the vessel wa ll. In addition, Ang II triggers responses in vascular smooth muscle cells that lead to proliferation, migration, and a phenotypic modulation resultin g in production of growth factors and extracellular matrix. While all of th ese effects contribute to neointima formation and development of atheroscle rotic lesions, Ang II may also be involved in acute complications of athero sclerosis by promoting plaque rupture and a hyperthrombotic state. Accordin gly, Ang II appears to have a central role in the pathophysiology of athero sclerosis. (C) 2000 Elsevier Science B.V. All rights reserved.