title: Angiotensin AT1 receptor over-expression in hypercholesterolaemia.
abstract: Angiotensin II mediates most of the biological effects of the renin-angiotensin system (RAS), such as vasoconstriction and cell proliferation, via stimulation of the angiotensin II type 1 (AT1) receptor. The AT1 receptor plays a central role in the pathogenesis of atherosclerosis and hypertension. In parallel, hypercholesterolaemia is a major risk factor for the development and progression of cardiovascular diseases. The underlying molecular events, however, are understood only partially. An important mechanism may be the interaction between hypercholesterolaemia and AT1 receptor expression in vascular tissue. Low-density lipoprotein (LDL) cholesterol leads to a profound increase in AT1 receptor expression in cultured vascular smooth muscle cells as well as in hypercholesterolaemic rabbits. This up-regulation is associated with an enhanced functional response upon stimulation with angiotensin II. Over-expression of the vascular AT1 receptor can also be observed in hypercholesterolaemic men and is prevented by treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. These findings may explain why hypercholesterolaemia is frequently associated with hypertension and why blockade of the RAS attenuates the progression of atherosclerosis.
authors.affiliation: Clinic III of Internal Medicine, University of Cologne, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Strehlow
authors.forename: S
authors.initials: S
authors.lastname: Wassmann
authors.forename: M
authors.initials: M
authors.lastname: Böhm
authors.forename: G
authors.initials: G
authors.lastname: Nickenig
mesh_terms: D000818:Animals; D008078:Cholesterol, LDL / Q000097:blood; D015536:Down-Regulation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D015854:Up-Regulation
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin