© 2000 American Heart Association, Inc.
Vascular Biology |
Monoclonal Antibody Against Vascular Cell Adhesion Molecule-1 Inhibits Neointimal Formation After Periadventitial Carotid Artery Injury in Genetically Hypercholesterolemic Mice
From the Atherosclerosis Research Center, Burns and Allen Research Institute, Division of Cardiology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, Calif, and the Department of Medicine (J.N.), Lund University, University Hospital MAS, Malmö, Sweden.
Correspondence to Jan Nilsson, MD, PhD, Department of Medicine, Malmö University Hospital, 205 02 Malmö, Sweden. E-mail jan.nilsson{at}medforsk.mas.lu.se
Abstract—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 
-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.
Key Words: vascular cell adhesion molecule-1 • inflammation • apoE knockout mice • neointimal formation
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