Angiotensin AT1 receptor over-expression in hypercholesterolaemia

Angiotensin II mediates most of the biological effects of the renin-angiote nsin system (RAS), such as vasoconstriction and cell proliferation, via sti mulation of the angiotensin II type 1 (AT1) receptor. The AT1 receptor play s a central role in the pathogenesis of atherosclerosis and hypertension. I n parallel, hypercholesterolaemia is a major risk factor for the developmen t and progression of cardiovascular diseases. The underlying molecular even ts, however, are understood only partially. An important mechanism may be t he interaction between hypercholesterolaemia and AT1 receptor expression in vascular tissue. Low-density lipoprotein (LDL) cholesterol leads to a prof ound increase in AT1 receptor expression in cultured vascular smooth muscle cells as well as in hypercholesterolaemic rabbits. This up-regulation is a ssociated with an enhanced functional response upon stimulation with angiot ensin 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 hyperte nsion and why blockade of the RAS attenuates the progression of atheroscler osis.