First Author | Dandapat A | Year | 2008 |
Journal | Biochem Biophys Res Commun | Volume | 366 |
Issue | 4 | Pages | 871-7 |
PubMed ID | 18037370 | Mgi Jnum | J:130186 |
Mgi Id | MGI:3771227 | Doi | 10.1016/j.bbrc.2007.11.061 |
Citation | Dandapat A, et al. (2008) Over-expression of angiotensin II type 2 receptor (agtr2) decreases collagen accumulation in atherosclerotic plaque. Biochem Biophys Res Commun 366(4):871-7 |
abstractText | Angiotensin (Ang) II, via type 1 receptor activation, exerts a significant role in atherogenesis and collagen synthesis. To test the hypothesis that Ang II type 2 receptor (AT2R) upregulation delivered with adeno-associated virus type 2 (AAV/AT2R) would inhibit collagen synthesis in atherosclerotic arteries, LDLR knockout mice were injected with AAV/AT2R and fed 4% cholesterol diet for 18 weeks. LDLR knockout mice treated with saline or AAV/Neo exhibited extensive vessel wall collagen accumulation, which was reduced by about 50% with AT2R over-expression. AT2R upregulation completely blocked the alterations in the expression of procollagen-I, osteopontin, fibronectin, CD68, and matrix metalloproteinases (MMP-2 and MMP-9), as well as phosphorylation of p38 and p44/42 MAPKs. Activity of superoxide dismutase was reduced in the LDLR KO mice and it increased with AT2R upregulation. This study demonstrates that AT2R over-expression reduces enhanced collagen accumulation, MMP expression and activity in atherosclerotic regions via inhibition of pro-oxidant signals. |