Hypercholesterolemia promotes leukocyte-dependent platelet adhesion in murine postcapillary venules.
OBJECTIVE
Leukocyte-platelet aggregates form in blood during the development of cardiovascular diseases, including atherosclerosis. The study determined whether leukocytes contribute to the platelet adhesion induced by hypercholesterolemia in postcapillary venules.


METHODS
Wild-type (WT) C57Bl/6 or CD18-deficient (CD18-/-) mice were placed on a normal (ND) or high-cholesterol (HC) diet for 2 weeks. Platelets isolated from ND, HC, or CD18-/- mice were fluorescently labeled with CFSE, and administered to either ND, HC, HC-CD18-/- or anti-neutrophil serum (HC-ANS)-treated mice. Rhodamine 6G was administered to label and visualize leukocytes. Intravital fluorescence microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules.


RESULTS
HC increased both leukocyte and platelet adhesion (relative to ND). Greater than 50% of adherent platelets in HC mice were bound to adherent leukocytes. When HC platelets were examined in HC-ANS-treated or HC-CD18-/- mice, leukocyte-dependent platelet adhesion was significantly attenuated. Conversely, when HC-CD18-/- platelets were observed in HC recipients both leukocyte-dependent and endothelium-dependent platelet adhesion was comparable to HC mice receiving WT platelets.


CONCLUSIONS
The findings demonstrate that the pro-thrombogenic phenotype assumed in the microvasculature during hypercholesterolemia is largely attributed to leukocyte-dependent platelet adhesion.
Tailor
Anitaben
A
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
Granger
D Neil
DN
D000818:Animals; D018821:CD18 Antigens / Q000097:blood / Q000235:genetics; D004036:Diet, Atherogenic; D006937:Hypercholesterolemia / Q000097:blood* / Q000209:etiology / Q000473:pathology; D007962:Leukocytes / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D010973:Platelet Adhesiveness; D014699:Venules / Q000473:pathology*
D018821:CD18 Antigens