Platelets in Atherosclerosis and Thrombosis
Rupture of an atherosclerotic plaque exposes a thrombogenic matrix, which instantly triggers platelet tethering and activation. We here delineate the sequence of events during arterial thrombus formation and dissect the specific role of the various platel
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Contents 1 Molecular Mechanisms of Platelet Accumulation Following Atherosclerotic Plaque Rupture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Tethering and Initial Activation of Platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Firm Adhesion and Aggregation of Platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Amplification of Platelet Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Crosstalk Between Platelets, Innate Immunity and Coagulation . . . . . . . . . . . . . . . . . . . . 2 Platelets in Atherosclerotic Lesion Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Platelet Adhesion to the Dysfunctional Endothelium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Proinflammatory Machinery of Platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Rupture of an atherosclerotic plaque exposes a thrombogenic matrix, which instantly triggers platelet tethering and activation. We here delineate the sequence of events during arterial thrombus formation and dissect the specific role of the various platelet receptors in this process. We also discuss the interplay of platelets with circulating immune cells, which support arterial thrombosis by fibrin formation in a process that involves extracellular nucleosomes. In the second part of this chapter we describe the role of platelets in atherosclerotic lesion formation. Platelets adhere to the dysfunctional endothelium early during atherogenesis. They contain a large machinery of proinflammatory molecules, which can be released upon their activation. This prepares the ground for subsequent leukocyte recruitment and infiltration, and boosts the inflammatory process of the arterial wall. Together, platelets play a critical role in both acute and chronic processes of the
C. Schulz • S. Massberg (*) Deutsches Herzzentrum and I. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany e-mail: [email protected]; [email protected] P. Gresele et al. (eds.), Antiplatelet Agents, Handbook of Experimental Pharmacology 210, DOI 10.1007/978-3-642-29423-5_5, # Springer-Verlag Berlin Heidelberg 2012
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vascular wall, which makes them an attractive target for pharmacological strategies to treat arterial thrombosis and, potentially, also atheroprogression. Key
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