Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression

Article

关键词: CIRCULATING PROCOAGULANT MICROPARTICLES;    PLATELET MICROPARTICLES;    ELEVATED LEVELS;    IN-VITRO;    ACTIVATION;    CELLS;    APOPTOSIS;    CAVEOLAE;    BLOOD;    INFECTION;   

DOI  :  10.1161/01.CIR.0000124065.31211.6E

来源: SCIE

【 摘 要 】

Background - Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation. The present study was designed to dissect the effects evoked by T lymphocyte - derived MPs on vascular function. Methods and Results - MPs were produced by treatment of the human lymphoid CEM T cell line with actinomycin D or phytohemagglutinin. Incubation of mouse aortic rings with 30 nmol/L MPs resulted in a time-dependent impairment of acetylcholine-induced relaxation of precontracted vessels, with a maximal reduction after 24 hours. MPs also impaired shear stress - induced dilatation of mouse small mesenteric arteries by affecting the nitric oxide ( NO) and prostacyclin but not the endothelium-derived hyperpolarizing factor components of the response. However, neither alteration of calcium signaling in response to agonists nor reduction of cyclooxygenase-1 expression accounted for the impairment of the NO and prostacyclin components of the endothelial response. The effect of MPs was rather because of a decrease in expression of endothelial NO synthase and an overexpression of caveolin-1. Furthermore, lymphocyte-derived MPs from diabetic patients or in vivo circulating MPs from either diabetic or HIV-infected patients reduced endothelial NO synthase expression. Finally, the effects of MPs on endothelial cells were not driven through CD11a/CD18 adhesion molecules or the Fas/FasL pathway. Conclusions - MPs from T cells induce endothelial dysfunction in both conductance and resistance arteries by alteration of NO and prostacyclin pathways. MPs regulate protein expression for endothelial NO synthase and caveolin-1. These data contribute to a better understanding of the deleterious effects of enhanced circulating MPs observed in disorders with cardiovascular or immune complications.

【 授权许可】

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