Premium
Hypercholesterolemia Promotes Leukocyte‐Dependent Platelet Adhesion in Murine Postcapillary Venules
Author(s) -
TAILOR ANITABEN,
GRANGER D. NEIL
Publication year - 2004
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680490503393
Subject(s) - platelet , intravital microscopy , cd18 , adhesion , chemistry , p selectin , platelet adhesiveness , immunology , platelet activation , cell adhesion molecule , microbiology and biotechnology , medicine , integrin alpha m , flow cytometry , microcirculation , biology , platelet aggregation , organic chemistry
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.