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Evaluation of VCAM-1 antibodies as therapeutic agent for atherosclerosis in apolipoprotein E-deficient mice

Title
Evaluation of VCAM-1 antibodies as therapeutic agent for atherosclerosis in apolipoprotein E-deficient mice
Authors
Park J.-G.Ryu S.Y.Jung I.-H.Lee Y.-H.Kang K.J.Lee M.-R.Lee M.-N.Sonn S.K.Lee J.H.Lee H.Oh G.T.Moon K.Shim H.
Ewha Authors
오구택심현보손성근이미니
SCOPUS Author ID
오구택scopus; 심현보scopus; 손성근scopus; 이미니scopusscopus
Issue Date
2013
Journal Title
Atherosclerosis
ISSN
0021-9150JCR Link
Citation
vol. 226, no. 2, pp. 356 - 363
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Objective: Blocking agents targeting cell adhesion molecules have been developed to prevent cardiovascular diseases such as atherosclerosis, whereas relatively little attention has been paid to the therapeutic potential of vascular cell adhesion molecule (VCAM)-1 as an inflammatory disease target. Two novel, fully human antibodies, H6 and 7H, against human VCAM-1 (hVCAM-1) were developed and tested to validate the hypothesis that blocking VCAM-1 ameliorates atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Methods and results: Treatment with H6 or 7H effectively inhibited VCAM-1 adhesion to inflammatory cells, and reduced RhoA activation and the production of reactive oxygen species in human umbilical cord vascular endothelial cells. As 7H showed binding affinity to both murine VCAM-1 (mVCAM-1) and hVCAM-1, the therapeutic effects of 7H in ApoE-/- mice were tested. After confirming specific in vivo binding activity of 7H to mVCAM-1, we showed that administering 7H resulted in significantly ameliorated plaque formation compared to administering a control antibody in ApoE-/- mice fed a Western diet for 12 weeks. Also, 7H treatment significantly reduced infiltration of CD45+ cells into plaques and reduced inflammation and improved plaque stability. Conclusion: These results indicate that the anti-VCAM-1 antibody attenuates atherosclerosis in ApoE-/- mice, improves plaque inflammation and stability as well as inhibiting the adhesion of inflammatory cell, and suggest that blocking VCAM-1 with a monoclonal antibody may be an effective means of anti-atherosclerotic therapy. © 2012 Elsevier Ireland Ltd.
DOI
10.1016/j.atherosclerosis.2012.11.029
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자연과학대학 > 생명과학전공 > Journal papers
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