Biomaterial Database

Hypercholesterolemia promotes leukocyte-dependent platelet adhesion in murine postcapillary venules. 2004

Anitaben Tailor, and D Neil Granger

Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.

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.

UI	MeSH Term	Description	Entries
D007962	Leukocytes	White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).	Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D010973	Platelet Adhesiveness	The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.	Adhesiveness, Platelet,Adhesivenesses, Platelet,Platelet Adhesivenesses
D004036	Diet, Atherogenic	A diet that contributes to the development and acceleration of ATHEROGENESIS.	Atherogenic Diet,Atherogenic Diets,Diets, Atherogenic
D006937	Hypercholesterolemia	A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.	Hypercholesteremia,Elevated Cholesterol,High Cholesterol Levels,Cholesterol Level, High,Cholesterol Levels, High,Cholesterol, Elevated,Cholesterols, Elevated,Elevated Cholesterols,High Cholesterol Level,Hypercholesteremias,Hypercholesterolemias,Level, High Cholesterol,Levels, High Cholesterol
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014699	Venules	The minute vessels that collect blood from the capillary plexuses and join together to form veins.	Venule
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out