| dc.description.abstract | Platelets are anucleate circulating blood cells. Activation of platelets is an important part of the complex mechanism of thrombosis and haemostasis. In an inactive state they circulate in blood and have the shape of disks with a smooth surface. Platelets are activated in the body when they come into contact with areas of endothelial damage or by activation of the coagulation cascade. Activated platelets change in shape, release their granule contents and form aggregates by sticking together. These shape changes may include conversion to a spherical shape, extension of pseudopodia or flattening on a surface during spreading - depending on the type of stimulus. The cytoskeleton is primarily responsible for regulating platelet shape [Fox 2001]. The platelet cytoskeleton is responsible for binding and positioning signaling molecules. Some parts of the cytoskeleton can bind signaling molecules in the unstimulated platelet, keeping them at specific submembranous locations where they can be triggered when the platelet is activated. Activated platelets bind to the plasma protein fibrinogen and this may result into a platelet aggregate. Next the platelet aggregate is stabilized by contraction of actin and myosin fragments in the platelets, leading to clot retraction. This physiological process allows platelet aggregation, contraction or spreading at sites of injury to prevent blood loss. In case of inappropriate or excessive platelet activation, however, this process results in blood flow defects due to thrombotic complications. The most common arterial thrombotic diseases are acute myocardial infarction and stroke. In addition, activated platelets are involved in inflammatory processes by expressing and releasing growth factors, chemokines and cytokines that attract and activate leukocytes and endothelial cells. Via these processes, platelets may be involved in inflammatory arthritis, adult respiratory distress syndrome, and tumor growth/metastasis. The role of the cytoskeleton in inflammatory processes remains to be delineated. A better understanding of how the cytoskeleton is regulated in platelets will provide insight in the regulation of platelet deformation, platelet adhesion, aggregation and clot retraction. In this review an overview of platelet physiology in relation to the major components of the cytoskeleton will be discussed. It includes mechanisms of platelet cytoskeleton reorganization upon stimulation and in resting platelets. Furthermore, important signaling molecules that are now known to be involved in inducing cytoskeletal reorganizations in platelets will be discussed. | |
