A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1

One crucial role of endothelium is to keep the innermost surface of a blood Vessel antithrombotic. However, the endothelium also expresses prothrombot ic molecules in response to various stimuli. The balance between the antith rombotic and prothrombotic nature of the endothelium is lost under certain conditions. During atherosclerosis, the attachment of platelets to the vess el surface has been suggested to promote the proliferation of smooth muscle cells and intimal thickening as well as to affect the prognosis of the dis ease directly through myocardial infarction and stroke. Dysfunctional endot helium, which is often a result of the action of oxidized low-density lipop rotein (OxLDL), tends to be more procoagulant and adhesive to platelets. He rein, we sought the possibility that the endothelial lectin-like OxLDL rece ptor-1 (LOX-1) is involved in the platelet-endothelium interaction and henc e directly in endothelial dysfunction. LOX-1 indeed worked as an adhesion m olecule for platelets. The binding of platelets was inhibited by a phosphat idylserine-binding protein, annexin V, and enhanced by agonists for platele ts. These results suggest that negative phospholipids exposed on activation on the surface of platelets are the epitopes for LOX-1. Notably, the bindi ng of platelets to LOX-1 enhanced the release of endothelin-1 from endothel ial cells, supporting the induction of endothelial dysfunction, which would , in turn, promote the atherogenic process. LOX-1 may initiate and promote atherosclerosis, binding not only OxLDL but also platelets.