Angiotensin type 2 receptor is expressed in murine atherosclerotic lesions and modulates lesion evolution

Abstract

Background - In the vasculature, the angiotensin type 2 (AT2) receptor (AT2R) exerts antiproliferative, antifibrotic, and proapoptotic effects. Normal adult animals have low AT2R expression; however, vascular injury and exposure to proinflammatory cytokines augment AT2R levels. We hypothesized that AT2R expression increases during initiation and progression of atherosclerosis. Methods and Results - Atherosclerotic lesions of apolipoprotein (Apo) E-/- mice contained AT2Rs, measured by real-time polymerase chain reaction and confirmed by immunohistochemistry. To test the consequences of this expression, male ApoE-/-, angiotensin II type 2 receptor-deficient (Agtr2 -), and ApoE-/-, wild-type (Agtr2+) mice consumed a high-cholesterol diet from 4 weeks of age. Ten weeks later, overall area and cellular composition of aortic arch lesions did not differ significantly among genotypes. After 16 weeks, ApoE-/-/Agtr2 +, but not ApoE-/-/Agtr2- mice had dramatic decreases in percent positive area of macrophages, smooth muscles, lipids, and collagen. Diminished bromodeoxyuridine incorporation and increased TUNEL staining accompanied these decreases. Conclusions - Thus, loss of AT 2R during the evolution of atherosclerotic lesions augmented the extent of cellularity of atherosclerotic lesions, establishing AT2R as a modulator of atherogenesis. © 2005 American Heart Association, Inc.