| Literature DB >> 18037370 |
Abhijit Dandapat1, Chang Ping Hu, Jiawei Chen, Yong Liu, Junaid A Khan, Francesco Remeo, Robert M Carey, Paul L Hermonat, Jawahar L Mehta.
Abstract
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.Entities:
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Year: 2007 PMID： 18037370 DOI： 10.1016/j.bbrc.2007.11.061
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575