Angiotensin Type 2 Receptor Is Expressed in Murine Atherosclerotic Lesions and Modulates Lesion Evolution

• Virna L. Sales

  From the Cardiovascular Division (V.L.S., M.A.L.-I., V.J.D., R.E.P.) and Donald W. Reynolds Cardiovascular Clinical Research Center (G.K.S., P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Dr Sales is now at the Department of Cardiac Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Mass; Dr Dzau is now at the Office of the Chancellor, Duke University Medical Center, Durham, NC.

• Galina K. Sukhova

  From the Cardiovascular Division (V.L.S., M.A.L.-I., V.J.D., R.E.P.) and Donald W. Reynolds Cardiovascular Clinical Research Center (G.K.S., P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Dr Sales is now at the Department of Cardiac Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Mass; Dr Dzau is now at the Office of the Chancellor, Duke University Medical Center, Durham, NC.

• Marco A. Lopez-Ilasaca

  From the Cardiovascular Division (V.L.S., M.A.L.-I., V.J.D., R.E.P.) and Donald W. Reynolds Cardiovascular Clinical Research Center (G.K.S., P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Dr Sales is now at the Department of Cardiac Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Mass; Dr Dzau is now at the Office of the Chancellor, Duke University Medical Center, Durham, NC.

• Peter Libby

  From the Cardiovascular Division (V.L.S., M.A.L.-I., V.J.D., R.E.P.) and Donald W. Reynolds Cardiovascular Clinical Research Center (G.K.S., P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Dr Sales is now at the Department of Cardiac Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Mass; Dr Dzau is now at the Office of the Chancellor, Duke University Medical Center, Durham, NC.

• Victor J. Dzau

  From the Cardiovascular Division (V.L.S., M.A.L.-I., V.J.D., R.E.P.) and Donald W. Reynolds Cardiovascular Clinical Research Center (G.K.S., P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Dr Sales is now at the Department of Cardiac Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Mass; Dr Dzau is now at the Office of the Chancellor, Duke University Medical Center, Durham, NC.

• Richard E. Pratt

  From the Cardiovascular Division (V.L.S., M.A.L.-I., V.J.D., R.E.P.) and Donald W. Reynolds Cardiovascular Clinical Research Center (G.K.S., P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Dr Sales is now at the Department of Cardiac Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Mass; Dr Dzau is now at the Office of the Chancellor, Duke University Medical Center, Durham, NC.

Abstract

Background— In the vasculature, the angiotensin type 2 (AT 2 ) receptor (AT 2 R) exerts antiproliferative, antifibrotic, and proapoptotic effects. Normal adult animals have low AT 2 R expression; however, vascular injury and exposure to proinflammatory cytokines augment AT 2 R levels. We hypothesized that AT 2 R expression increases during initiation and progression of atherosclerosis. Methods and Results— Atherosclerotic lesions of apolipoprotein (Apo) E −/− mice contained AT 2 Rs, 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 2 R during the evolution of atherosclerotic lesions augmented the extent of cellularity of atherosclerotic lesions, establishing AT 2 R as a modulator of atherogenesis.

Journal

• Circulation

  Circulation 112 (21), 3328-3336, 2005-11-22

  Ovid Technologies (Wolters Kluwer Health)

Keywords

• Physiology (medical)
• Cardiology and Cardiovascular Medicine

Details

• CRID: 1362544418996549888
• NII Article ID: 30022671313
• DOI: 10.1161/circulationaha.105.541714
• ISSN: 15244539
• ISSN: 00097322
• ISSN: http://id.crossref.org/issn/00097322
• Web Site: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.105.541714
• Data Source:
  • Crossref
  • CiNii Articles