Oxidized LDL-Activated Platelets Induce Vascular Inflammation

Abstract

Platelets are involved in the initiation of atherosclerosis by adherence to inflamed endothelium. Monocytes bind to these platelets and transmigrate into the vessel wall, transforming into macrophages and foam cells. We have previously shown that lipid-laden platelets are phagocytosed by macrophages. In this study we investigated the functional consequences of oxidized low-density lipoprotein (oxLDL) uptake on platelet function and interaction with the endothelium. Human platelets were isolated from healthy donors and activated by adenosine diphosphate. Immunofluorescence microscopy and flow cytometry revealed that oxLDL is located intracellularly in vesicles. With mepacrine costaining and confocal microtomography, we were able to identify dense granules as the vesicles that contain oxLDL. OxLDL-laden platelets induced intercellular adhesion molecule 1 expression in endothelial cells more than exogenous native LDL, oxLDL, and oxLDL-negative platelets. Furthermore, oxLDL-laden platelets induced foam cell development from CD34(+) progenitor cells. On endothelial regeneration, oxLDL-laden platelets had the opposite effect: The number of CD34(+) progenitor cells (colony-forming units) able to transform into endothelial cells was significantly reduced in the presence of oxLDL-platelets, whereas native LDL had no effect. Our results demonstrate that activated platelets internalize oxLDL and that oxLDL-laden platelets activate endothelium, inhibit endothelial regeneration, and promote foam cell development. Platelet oxLDL contributes significantly to vascular inflammation and is able to promote atherosclerosis.