on January 16, 2003
Published online before print January 16, 2003, doi: 10.1161/01.ATV.0000056742.97580.79
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Submitted on December 3, 2002
Accepted on January 7, 2003
Hypercholesterolemia Promotes P-Selectin-Dependent Platelet-Endothelial Cell Adhesion in Postcapillary Venules
Anitaben Tailor and D. Neil Granger *
From the Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, La.
* To whom correspondence should be addressed. E-mail: dgrange{at}lsuhsc.edu.
Objective--The objectives of this study were to determine whether hypercholesterolemia promotes platelet-endothelial cell (P/E) adhesion in murine postcapillary venules and define the contributions of endothelial or platelet associated P-selection to hypercholesterolemia-induced P/E interactions.
Methods and Results--Wild-type (WT) or P-selectin deficient (P-sel-/-) platelets were isolated and labeled with the fluorochrome CFSE and administered to either WT or P-sel-/- mice placed on a normal diet (ND) or high cholesterol diet (HCD). Intravital videomicroscopy was used to quantify platelet saltation and firm adhesion. HCD-WT mice exhibited a time-dependent increase in P/E cell interactions (relative to ND-WT). Flow cytometry revealed an increased expression of P-selectin on circulating platelets of HCD-WT mice at 2 weeks compared with ND-WT mice. When WT platelets were monitored in HCD-P-sel-/- mice, P/E adhesion was dramatically reduced. However, when P-sel-/- platelets were monitored in HCD-WT recipients, P/E adhesive interactions were reduced even further, comparable to ND-WT mice.
Conclusions--These results indicate that elevated cholesterol levels promote P/E adhesion in postcapillary venules and that whereas both endothelial and platelet P-selectin contribute to hypercholesterolemia-induced recruitment of platelets, platelet-associated P-selectin seems to play a more important role in producing the prothrombogenic phenotype in venules.
Key words: hypercholesterolemia • platelets • P-selectin • endothelial cells • thrombogenesis
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