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


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.
Sales
Virna L
VL
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. virna.sales@childrens.harvard.edu
Sukhova
Galina K
GK
Lopez-Ilasaca
Marco A
MA
Libby
Peter
P
Dzau
Victor J
VJ
Pratt
Richard E
RE
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002455:Cell Division; D003094:Collagen / Q000378:metabolism; D004036:Diet, Atherogenic; D005260:Female; D015870:Gene Expression / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics* / Q000378:metabolism*; D014657:Vasculitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D001057:Apolipoproteins E; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D003094:Collagen