Published online before print January 16, 2003, doi: 10.1161/01.ATV.0000056742.97580.79
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© 2003 American Heart Association, Inc.
Thrombosis |
Hypercholesterolemia Promotes P-Selectin–Dependent Platelet–Endothelial Cell Adhesion in Postcapillary Venules
From the Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, La.
Correspondence to D. Neil Granger, PhD, Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130-3982. 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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