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

Journal Article

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 AT2R during the evolution of atherosclerotic lesions augmented the extent of cellularity of atherosclerotic lesions, establishing AT2R as a modulator of atherogenesis.

Full Text

Duke Authors

Cited Authors

  • Sales, VL; Sukhova, GK; Lopez-Ilasaca, MA; Libby, P; Dzau, VJ; Pratt, RE

Published Date

  • November 22, 2005

Published In

Volume / Issue

  • 112 / 21

Start / End Page

  • 3328 - 3336

PubMed ID

  • 16286588

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.105.541714

Language

  • eng

Conference Location

  • United States