Functional relevance of HPA-1 and {α2 [alpha2] 807C-T platelet receptor polymorphisms under standardized in-vitro blood flow conditions [Elektronische Ressource] / vorgelegt von Robert Loncar

Aus dem Institut für Hämostaseologie und Transfusionsmedizin der Heinrich-Heine-Universität Düsseldorf Direktor: Prof. Dr. R.E. Scharf Functional Relevance of HPA-1 and α2 807C/T Platelet Receptor Polymorphisms Under Standardized In-Vitro Blood Flow Conditions Habilitationsschrift der Hohen Medizinischen Fakultät der Heinrich-Heine-Universität Düsseldorf zur Erlangung der Venia legendi für das Fach Transfusionsmedizin vorgelegt von Dr.rer.nat.(HR) Robert Loncar Düsseldorf, 2006 2 Content 1. Introduction 5 1.1. Pathogenesis of arterial thrombosis 6 1.1.1. Central role of platelets in arterial thrombosis 6 1.1.2. Specific platelet receptor interplay during thrombus formation 7 1.2 Integrin αIIb β3 (GPIIb/IIIa) 10 1.2.1 Structure and physiological role 11 1.3. Integrin α2 β1 (GPIa/IIa) 14 1.3.1. 14 1.4. Platelet receptor polymorphism 16 1.4.1. 18 HPA-1 polymorphism of αIIb β3 1.4.2. α2 807C/T polymorphism of α2 β1 19 1.5. Platelet receptor polymorphisms and their role in arterial thrombosis, clinical and epidemiological evidence 20 1.6. Shear force and shear stress in arterial thrombosis 23 1.6.1. Basic rheological blood features 23 1.6.2 Biological effects of shear stress 28 1.6.3. Experimental model of the vascular system 31 2. Goal of the study 33 3. Subjects and methods 35 3.1. Subjects 35 3.2. Blood collection and preparation 35 3.3. Determination of HPA-1 and α2 807 CT genotypes 35 3.