Platelet-leukocyte interactions link inflammatory and thromboembolic events in ischemic stroke

Abstract

Stroke is a common and often fatal event, and, in survivors, it is accompanied by a high risk of recurrence. Ischemic stroke is associated with abnormal platelet activity and thrombus formation. In addition to their roles in the development of acute thrombi, platelets serve as a bridge for leukocytes within the vasculature. Myeloid leukocytes are critical mediators of atherosclerosis and atherothrombosis. Interactions between platelets and leukocytes foster an inflammatory and thrombotic milieu that influences lesion progression, facilitates plaque rupture, and triggers thrombus formation and embolization. Accordingly, antiplatelet agents, including aspirin, dipyridamole, and clopidogrel, are recommended therapies for most patients with a history of stroke. In addition to mitigating thrombosis, antiplatelet drugs have direct and indirect effects on inflammation, which may translate to enhanced clinical efficacy.

Figure 1

Schematic depicting interactions of platelets and leukocytes in a vulnerable atherosclerotic vessel. In normal situations, endothelial cells lining the vasculature provide an anti-inflammatory barrier that prevents platelets (light blue) and leukocytes from adhering to the vessel wall. In advanced atherosclerotic lesions, however, endothelial dysfunction and/or plaque rupture triggers abnormal platelet adherence to the damaged area. Display of P-selectin on the surface of adherent platelets and inflamed endothelium, in combination with exposed extracellular matrix, triggers a cascade of events that include monocyte adherence and emigration into the vascular wall. Adherence of platelets to monocytes also triggers the synthesis of proinflammatory mediators that may impact atherothrombotic events in secondary stroke and related cardiovascular disorders.