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

Background--We tested the hypothesis that apolipoprotein (apo)E-deficient ( apoE-/-) mice with targeted disruption of the intercellular adhesion molecu le-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-/- m ice were fed an atherogenic Western diet for 5 weeks and underwent wire den udation of the left common carotid artery after 1 week of feeding. The abse nce 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 macrophage s were found in the neointima and media of apoE-/- and apoE-/- ICAM-1-/- mi ce. 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-sele ctin, but not ICAM-1, markedly reduces plaque area and suggest that P-selec tin is critical for monocyte recruitment to sites of neointima formation af ter arterial injury.