Central role of the AT(1)-receptor in atherosclerosis.
The renin-angiotensin system plays a major role in the pathogenesis of atherosclerosis. Most known effects of angiotensin II are mediated via activation of the AT(1)-receptor, which is in turn influenced to a great degree by levels of expression of the AT(1)-receptor. AT(1)-receptor activation is not only involved in vasoconstriction, water and salt homoeostasis and control of other neurohumoral systems, but also induces reactive oxygen species production, cellular hypertrophy and hyperplasia and apoptosis. Expression of this G-protein-coupled receptor is regulated by multiple factors. Among other conditions, oestrogen deficiency and hypercholesterolaemia increase AT(1)-receptor expression. Experimental data suggest that this augments the actions of angiotensin II, contributes to endothelial dysfunction, increases vascular production of reactive oxygen species, and via these mechanisms promotes atherosclerosis. Because of this, AT(1)-receptor regulation is likely to be critical in the development and progression of vascular lesions. Interventional studies demonstrated that ACE inhibitors which reduce AT(1)-receptor activation, improve endothelial dysfunction and inhibit onset and progression of atherosclerosis. The more specific AT(1)-receptor antagonists have also been shown to decrease blood pressure, protect renal function and to improve endothelial function. Thus, there is compelling evidence that AT(1)-receptor activation participates in the pathogenesis of atherosclerosis, and more importantly, that treatment regimens aiming at inhibition of AT(1)-receptor activation are promising anti-atherosclerotic therapeutic options.
Nickenig
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Medizinische Klinik und Poliklinik Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany. nickenig@med-in.uni-sb.de
D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology*
D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin