Absence of P-selectin, but not intercellular adhesion molecule-1, attenuates neointimal growth after arterial injury in apolipoprotein E-deficient mice

David Manka, Robert G. Collins, Klaus Ley, Arthur L. Beaudet, Ian J. Sarembock

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1000-1005
Number of pages6
JournalCirculation
Volume103
Issue number7
DOIs
StatePublished - Feb 20 2001
Externally publishedYes

Keywords

  • Arteries
  • Atherosclerosis
  • Cell adhesion molecules
  • Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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