Understanding regulation of platelet function represents the long-term objectives of the proposed research, and which has direct relevance to the roles of platelets in hemostasis, the development of atherosclerosis, and in bleeding disorders. The major specific aim for the fellowship is to test the hypothesis that platelet adhesion to Collagen requires the participation of both the 2beta, integrin and glycoprotein VI (GpVI) as collagen receptors. Research design involves several approaches. First, platelet adhesion kinetics to collagen and to a collagen-related peptide (CRP) will be evaluated in the presence of specific receptor-blocking antibodies available to the host, and under arterial flow conditions using special apparatus designed by the applicant. Second, to evaluate signalling characteristics elicited by conditions designed to favour one receptor over another, specially for activation of protein kinase C and the tyrosine kinases, syk and pp125 FAK. Lastly, genetically-modified mice deficient in defined signalling proteins such as the tyrosine kinase syk, FcR-chain, will be tested for CRP and collagen-adhesion characteristics under high-shear versus low- shear conditions.
|Polanowska-Grabowska, Renata; Gibbins, Jonathan M; Gear, Adrian R L (2003) Platelet adhesion to collagen and collagen-related peptide under flow: roles of the [alpha]2[beta]1 integrin, GPVI, and Src tyrosine kinases. Arterioscler Thromb Vasc Biol 23:1934-40|