Hypercholesterolemia Promotes Leukocyte-Dependent Platelet Adhesion in Murine Postcapillary Venules

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Abstract
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.

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