title: Evaluation of VCAM-1 antibodies as therapeutic agent for atherosclerosis in apolipoprotein E-deficient mice.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-dong, Seodaemoon-gu, Seoul 120-750, Republic of Korea.
authors.forename: Jong-Gil
authors.initials: JG
authors.lastname: Park
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Ryu
authors.forename: In-Hyuk
authors.initials: IH
authors.lastname: Jung
authors.forename: You-Han
authors.initials: YH
authors.lastname: Lee
authors.forename: Kyung Jae
authors.initials: KJ
authors.lastname: Kang
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Lee
authors.forename: Mi-Ni
authors.initials: MN
authors.lastname: Lee
authors.forename: Seong Keun
authors.initials: SK
authors.lastname: Sonn
authors.forename: Jeong Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Kyungduk
authors.initials: K
authors.lastname: Moon
authors.forename: Hyunbo
authors.initials: H
authors.lastname: Shim
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000188:drug therapy*; D002448:Cell Adhesion / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000188:drug therapy; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1