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The Effect of Soluble RAGE on Inhibition of Angiotensin II-Mediated Atherosclerosis in Apolipoprotein E Deficient Mice

Authors
 Dajeong Lee ; Kyung Hye Lee ; Sungha Park ; Soyeon Lim ; Ji Hyung Chung ; Soyoung Cho ; Taewon Jin ; Soo Hyuk Kim ; Hyelim Park 
Citation
 PLoS One, Vol.8(8) : e69669, 2013 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2013
Abstract
BACKGROUND: The cross talk between RAGE and angiotensin II (AngII) activation may be important in the development of atherosclerosis. Soluble RAGE (sRAGE), a truncated soluble form of the receptor, acts as a decoy and prevents the inflammatory response mediated by RAGE activation. In this study, we sought to determine the effect of sRAGE in inhibiting AngII-induced atherosclerosis in apolipoprotein E knockout mice (Apo E KO). METHODS AND RESULTS: 9 week old Apo E KO mice were infused subcutaneously with AngII (1 µg/min/kg) and saline for 4 weeks using osmotic mini-pumps. The mice were divided into 4 groups 1. saline infusion and saline injection; 2. saline infusion and sRAGE injection; 3. AngII infusion and saline injection; 4. AngII infusion and sRAGE injection. Saline or 0.5 µg, 1 µg, to 2 µg/day/mouse of sRAGE were injected intraperitoneally daily for 28 days. We showed that atherosclerotic plaque areas in the AngII-infused Apo E KO mice and markers of inflammation such as RAGE, ICAM-1, VCAM-1, and MCP-1 were increased in aorta compared to that of the Apo E KO mice. However, the treatment of 0.5 µg, 1 µg, and 2 µg of sRAGE in AngII group resulted in the dose-dependent decrease in atherosclerotic plaque area. We also demonstrated that sRAGE decreased RAGE expression level as well as inflammatory cytokines and cell adhesion molecules in AngII or HMGB1 treated-rat aorta vascular smooth muscle cells. CONCLUSION: The results demonstrated that partical blockade of RAGE activation by sRAGE prevent AngII -induced atherosclerosis. Therefore these results suggested that first, RAGE activation may be important in mediating AngII-induced atherogenesis, and second, AngII activation is a major pathway in the development of atherosclerosis. Taken together, results from this study may provide the basis for future anti- atherosclerotic drug development mediated through RAGE activation.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/87441
DOI
10.1371/journal.pone.0069669
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Cardiovascular Product Evaluation Center
1. 연구논문 > 5. Research Institutes > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
Yonsei Authors
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