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

Jong Gil Park, Su Yeon Ryu, In Hyuk Jung, You Han Lee, Kyung Jae Kang, Mi Ran Lee, Mi Ni Lee, Seong Keun Sonn, Jeong Hwa Lee, Hang Lee, Goo Taeg Oh, Kyungduk Moon, Hyunbo Shim

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish
Pages (from-to)356-363
Number of pages8
JournalAtherosclerosis
Volume226
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Antibody
  • Atherosclerosis
  • Inflammation
  • Plaque stability
  • Vascular cell adhesion molecule-1

Fingerprint

Dive into the research topics of 'Evaluation of VCAM-1 antibodies as therapeutic agent for atherosclerosis in apolipoprotein E-deficient mice'. Together they form a unique fingerprint.

Cite this