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 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.


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.
Manka
D
D
Departments of Biomedical Engineering, Cardiovascular Division, University of Virginia Health Sciences Center, Charlottesville, VA, USA.
Collins
R G
RG
Ley
K
K
Beaudet
A L
AL
Sarembock
I J
IJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
D000199:Actins; D001057:Apolipoproteins E; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1