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Publication : Absence of p-selectin, but not intercellular adhesion molecule-1, attenuates neointimal growth after arterial injury in apolipoprotein e-deficient mice.

First Author  Manka D Year  2001
Journal  Circulation Volume  103
Issue  7 Pages  1000-5
PubMed ID  11181476 Mgi Jnum  J:103301
Mgi Id  MGI:3609100 Doi  10.1161/01.cir.103.7.1000
Citation  Manka D, et al. (2001) Absence of p-selectin, but not intercellular adhesion molecule-1, attenuates neointimal growth after arterial injury in apolipoprotein e-deficient mice. Circulation 103(7):1000-5
abstractText  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.
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