Monoclonal antibody against vascular cell adhesion molecule-1 inhibits neointimal formation after periadventitial carotid artery injury in genetically hypercholesterolemic mice.
Vascular cell adhesion molecule (VCAM)-1 is induced in smooth muscle cells after arterial injury, in which it has been implicated in the recruitment of inflammatory cells to the site of injury. To investigate the effect of hypercholesterolemia on VCAM-1 induction after injury and the role of VCAM-1 in neointimal response to injury, we injured the carotid artery of wild-type and apolipoprotein E null (KO) mice fed normal and high cholesterol chow. We demonstrate a graded response of VCAM-1 induction as well as monocyte/macrophage infiltration by immunohistochemistry 3 days after injury that correlated with increasing circulating cholesterol levels. Three weeks after injury, KO mice fed high cholesterol chow (KO HC group) had a significantly greater neointimal formation compared with wild-type and KO mice fed normal chow (P<0.05). Inhibition of VCAM-1 function in the KO HC group by monoclonal antibody treatment significantly reduced monocyte/macrophage infiltration and neointimal formation. There was reduced alpha-actin expression in KO HC mice 7 days after injury that was partially inhibited by VCAM-1 antibody treatment. Cell migration in an in vitro injury model was partially inhibited by monoclonal VCAM-1 antibody treatment. We propose an additional role for VCAM-1 in smooth muscle cell activation and neointimal formation after injury.
Oguchi
S
S
Atherosclerosis Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA, USA.
Dimayuga
P
P
Zhu
J
J
Chyu
K Y
KY
Yano
J
J
Shah
P K
PK
Nilsson
J
J
Cercek
B
B
D000199:Actins / Q000032:analysis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000235:genetics*; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D006937:Hypercholesterolemia / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D017539:Tunica Intima / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology / Q000473:pathology
D000199:Actins; D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol