Unravelling the interactions between leukocytes and platelet-derived extracellular vesicles in atherosclerosis

[摘要] Atherosclerosis is a progressive inflammatory disease, characterized by accumulation of fatty deposits and degenerative material in the wall of arteries forming a growing atheromatous plaque that upon rupture may cause thrombosis. An essential step in atherosclerosis progression is monocyte recruitment to the inflamed vessel wall and subsequent uptake of fats that upon apoptosis contribute to further inflammation. Increased levels of PEV have been reported to circulate in atherosclerosis patients, suggesting that they possibly contribute to disease development. We demonstrated that PEV are released from platelets upon activation through various routes. PEV contain adhesion receptors such as GPIb and GPIIb and may also contain a mitochondrion. In vitro platelet activation in the blood results in PEV release that preferentially form aggregates with monocytes. Monocytes can internalize PEV through various endocytic mechanisms. PEV aggregation with monocytes was functional as monocytes that had aggregated with PEV exhibited increased recruitment to the carotid endothelium in mice with established atherosclerosis in vivo. We also generated and characterized a new mouse model, which is athero-prone and inducible of platelet clearance. This mouse will help elucidate the acute and chronic effects of injected PEV in atherosclerosis, independently of platelets. Our observations are important because they have identified a novel thrombo-inflammatory pathway of leukocyte recruitment to the vessel wall, that may be relevant in atherosclerosis.

[发布机构] University:University of Birmingham;Department:Institute of Cardiovascular Sciences

[关键词] R Medicine;RC Internal medicine