(Circulation. 2001;103:1000.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Absence of P-Selectin, but Not Intercellular Adhesion Molecule-1, Attenuates Neointimal Growth After Arterial Injury in Apolipoprotein E–Deficient Mice
From the Departments of Biomedical Engineering (D.M., K.L.) and Medicine (I.J.S.), Cardiovascular Division, University of Virginia Health Sciences Center, Charlottesville, and the Department of Molecular and Human Genetics (R.G.C., A.L.B.), Baylor College of Medicine, Houston, Tex.
Correspondence to Ian J. Sarembock, MD, Cardiovascular Division, University of Virginia Health System, Box 158, Charlottesville, VA 22908. E-mail ijs4s{at}virginia.edu
Background—We tested the hypothesis that apolipoprotein (apo)E-deficient (apoE-/-) mice with targeted disruption of the intercellular adhesion molecule-1 (ICAM-1) or P-selectin gene (apoE-/- ICAM-1-/- or apoE-/- P-selectin-/- mice, respectively) are protected from neointima formation after arterial injury through inhibition of monocyte trafficking to sites of endothelial denudation.
Methods and Results—ApoE-/-, apoE-/- ICAM-1-/-, or apoE-/- P-selectin-/- mice were fed an atherogenic Western diet for 5 weeks and underwent wire denudation of the left common carotid artery after 1 week of feeding. The absence of P-selectin in apoE-/- mice inhibited neointima formation by 94% (P<0.0001) after arterial injury and reduced the intima-to-media ratio compared with the presence of P-selectin in apoE-/- mice. ICAM-1 deficiency did not protect against plaque formation after injury. Large numbers of macrophages were found in the neointima and media of apoE-/- and apoE-/- ICAM-1-/- mice. In contrast, almost no macrophages were found in the media or neointima of injured apoE-/- P-selectin-/- arteries.
Conclusions—These findings demonstrate that the complete absence of P-selectin, but not ICAM-1, markedly reduces plaque area and suggest that P-selectin is critical for monocyte recruitment to sites of neointima formation after arterial injury.
Key Words: arteries • cell adhesion molecules • inflammation • atherosclerosis
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