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Article

Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis

  • Authors:
    • Chang Hoon Ha
    • Sunghyen Kim
    • Jihwa Chung
    • Shung Hyen An
    • Sungha Park
    • Donghoon Choi
    • Kihwan Kwon
  • View Affiliations / Copyright

    Affiliations: Medical Research Institute, Ewha Womans University, Yangcheon-gu, Seoul 158-710, Republic of Korea, Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seodaemun-gu, Seoul 120-752, Republic of Korea, Department of Internal Medicine, Cardiology Division, School of Medicine, Ewha Womans University, Yangcheon-gu, Seoul 158-710, Republic of Korea
  • Pages: 373-380
    |
    Published online on: May 27, 2013
       https://doi.org/10.3892/ijmm.2013.1393
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Abstract

Soluble receptor for advanced glycation end products RAGE (sRAGE), a secretory form of RAGE, plays an important role in suppressing RAGE signals that induce pro-inflammatory gene activation in a range of inflammatory diseases, such as Alzheimer's disease, complications of diabetes mellitus and atherosclerosis. Recent studies have suggested that fluid shear stress generated by laminar blood flow protects blood vessels from atherosclerosis, whereas low and oscillatory shear stress (OSS) generated by disturbed blood flow causes atherosclerosis. Although RAGE levels are increased in atherosclerotic plaque, the regulatory mechanisms of sRAGE in the occurrence of atherosclerotic plaque induced by disturbed blood flow remain largely unknown. This study aimed to determine the effects of sRAGE as a competitive inhibitor of RAGE in atherogenesis induced by disturbed blood flow. To determine the role of sRAGE in atherosclerosis induced by disturbed blood flow, we used a mouse model of partial carotid artery ligation using ApoE-/- and C57BL/6 mice. Our results revealed that the expression of RAGE was significantly increased in the region of atherosclerotic plaque and that treatment with sRAGE attenuated the development of plaque formation. We found that the expression levels of RAGE and high mobility group box 1 (HMGB1), the agonistic ligand of RAGE, were significantly increased in human umbilical vein endothelial cells (HUVECs) under shear stress conditions induced by disturbed blood flow and suppressed following treatment with sRAGE. We further observed that treatment with sRAGE decreased the expression of vascular cell adhesion molecule‑1 (VCAM-1) and markedly attenuated monocyte-endothelial cell adhesion. Taken together, our results reveal that sRAGE exerts anti-atherogenic effects by blocking the activation of the RAGE signaling pathway induced by disturbed blood flow and may thus be a potential therapeutic target for the prevention of atherosclerosis.
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Copy and paste a formatted citation
Spandidos Publications style
Ha CH, Kim S, Chung J, An SH, Park S, Choi D and Kwon K: Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis. Int J Mol Med 32: 373-380, 2013.
APA
Ha, C.H., Kim, S., Chung, J., An, S.H., Park, S., Choi, D., & Kwon, K. (2013). Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis. International Journal of Molecular Medicine, 32, 373-380. https://doi.org/10.3892/ijmm.2013.1393
MLA
Ha, C. H., Kim, S., Chung, J., An, S. H., Park, S., Choi, D., Kwon, K."Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis". International Journal of Molecular Medicine 32.2 (2013): 373-380.
Chicago
Ha, C. H., Kim, S., Chung, J., An, S. H., Park, S., Choi, D., Kwon, K."Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis". International Journal of Molecular Medicine 32, no. 2 (2013): 373-380. https://doi.org/10.3892/ijmm.2013.1393
Copy and paste a formatted citation
x
Spandidos Publications style
Ha CH, Kim S, Chung J, An SH, Park S, Choi D and Kwon K: Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis. Int J Mol Med 32: 373-380, 2013.
APA
Ha, C.H., Kim, S., Chung, J., An, S.H., Park, S., Choi, D., & Kwon, K. (2013). Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis. International Journal of Molecular Medicine, 32, 373-380. https://doi.org/10.3892/ijmm.2013.1393
MLA
Ha, C. H., Kim, S., Chung, J., An, S. H., Park, S., Choi, D., Kwon, K."Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis". International Journal of Molecular Medicine 32.2 (2013): 373-380.
Chicago
Ha, C. H., Kim, S., Chung, J., An, S. H., Park, S., Choi, D., Kwon, K."Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis". International Journal of Molecular Medicine 32, no. 2 (2013): 373-380. https://doi.org/10.3892/ijmm.2013.1393
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