Apoptosis and vascular cell activation are main contributors to the release of procoagulant microparticles (MPs), deleterious partners in atherothrombosis. Elevated levels of circulating platelet, monocyte, or endothelial-derived MPs are associated with most of the cardiovascular risk factors and appear indicative of poor clinical outcome. In addition to being a valuable hallmark of vascular cell damage, MPs are at the crossroad of atherothrombosis processes by exerting direct effects on vascular or blood cells. Under pathological circumstances, circulating MPs would support cellular cross-talk leading to vascular inflammation and tissue remodeling, endothelial dysfunction, leukocyte adhesion, and stimulation. Exposed membrane phosphatidylserine and functional tissue factor (TF) are 2 procoagulant entities conveyed by circulating MPs. At sites of vascular injury, P-selectin exposure by activated endothelial cells or platelets leads to the rapid recruitment of MPs bearing the P-selectin glycoprotein ligand-1 and blood-borne TF, thereby triggering coagulation. Within the atherosclerotic plaque, sequestered MPs constitute the main reservoir of TF activity, promoting coagulation after plaque erosion or rupture. Lesion-bound MPs, eventually harboring proteolytic and angiogenic effectors are additional actors in plaque vulnerability. Pharmacological strategies aimed at modulating the release of procoagulant MPs appear a promising therapeutic approach of both thrombotic processes and bleeding disorders.
Morel et al. (Fri,) studied this question.