Novel Targets for Platelet Inhibition
Atherothrombosis often underlies coronary artery disease, stroke, and peripheral arterial disease. Antiplatelet drugs have come to the forefront of prophylactic treatment of atherothrombotic disease. Dual antiplatelet therapy of aspirin plus clopidogrel—t
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Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Identification of Novel Targets via Platelet Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 General Concept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Tyrosine Phosphorylated Immunoglobulin Receptor: G6B . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Actin-Binding Adaptor: HIP-55 in Thrombin Activated Platelets . . . . . . . . . . . . . . . . . . 2.4 Aldose Reductase-AR and Disulfide Isomerase: ERp57 in GPVI Signaling . . . . . . . 3 Identification of Novel Targets via Studies in Patients with Inherited Platelet Disorders 3.1 General Concept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Bleeding in Patients with PACAP Overexpression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Inhibitors of cAMP: Studies from Gsalpha/RGS2 Defective Patients . . . . . . . . . . . . . . 4 Identification of Novel Targets via Large-Scale Genetic Studies in Healthy Subjects . . 4.1 General Concept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Candidate Gene Association Studies Using a Genomics Approach and Functional Platelet Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Genome-Wide Association Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Characterization of Novel Targets via Functional Genomics in Animal Models . . . . . . . . 5.1 General Concept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Mouse Model for Ecto-Nucleotidase: CD39/NTPDaseI . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Mouse Models for Growth Arrest-Specific Gene 6: Gas6 and Its Receptors Tyro3, Axl, and Mer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Mouse Models for Leptin and Leptin Receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5 Mouse Models for Platelet Receptor Function Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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K. Freson (*) Center for Molecular and Vascular Biology, University of Leuven, Herestraat 49, 3000 Leuven, Belgium e-mail: [email protected] C. Van Geet Center for Molecular and Vascular Biology, University of Leuven, Herestraat 49, 3000 Leuven, Belgium Department of Pediatrics, University of Leuven, Herestraat 49, 3000 Leuven, Belgium P. Gresele et al. (eds
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