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.