Hypercholesterolemia promotes P-selectin-dependent platelet-endothelial cell adhesion in postcapillary venules.
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.


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.
Tailor
Anitaben
A
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130-3982, USA. dgrange@lsuhsc.edu
Granger
D Neil
DN
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000473:pathology*; D002448:Cell Adhesion; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000473:pathology*; D018056:Hemorheology; D006937:Hypercholesterolemia / Q000097:blood / Q000473:pathology*; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000502:physiology*; D019851:Thrombophilia / Q000209:etiology; D014699:Venules / Q000473:pathology*
D002791:Cholesterol, Dietary; D019007:P-Selectin; D002784:Cholesterol