Enhanced plasma levels of LIGHT in unstable angina possible pathogenic role in foam cell formation and thrombosis

Article

关键词: ACUTE CORONARY SYNDROMES;    MONOCYTE-DERIVED MACROPHAGES;    SCAVENGER RECEPTORS;    SIGNALING PATHWAYS;    TNF SUPERFAMILY;    CD40 LIGAND;    ATHEROSCLEROSIS;    LIPOPROTEINS;    CYTOKINES;    INFLAMMATION;   

DOI  :  10.1161/CIRCULATIONAHA.105.544676

来源: SCIE

【 摘 要 】

Background-Numerous studies have demonstrated the ability of oxidized LDL [( ox) LDL] to promote an inflammatory response in macrophages. Several inflammatory mediators have been reported to increase after oxLDL stimulation of such cells, but their relative importance is still unknown. In the present study, we used microarrays to identify genes in THP-1 macrophages that were upregulated by oxLDL. Methods and Results-Our main findings were as follows. In a microarray screening experiment, we identified LIGHT, a ligand in the tumor necrosis factor superfamily, as one of the genes that were markedly upregulated in oxLDL-stimulated THP-1 macrophages. We showed significantly raised plasma levels of LIGHT in patients with stable angina (n = 40) and particularly in those with unstable angina ( n = 40) compared with healthy controls ( n = 20), which underscores the clinical relevance of the in vitro finding. We also showed that LIGHT enhanced lipid accumulation in oxLDL-stimulated THP-1 macrophages, possibly through upregulation of class A scavenger receptor (SR-A). This increased lipid accumulation was accompanied by enhanced expression of tissue factor and plasminogen activator inhibitor-1, as well as enhanced thrombin formation, transforming macrophages into a prothrombotic phenotype. The LIGHT-mediated increase in SR-A, tissue factor, and plasminogen activator inhibitor-1 was also seen in human monocyte-derived macrophages. Finally, the LIGHT-mediated enhancement of SR-A and TF expression appears to involve nuclear factor-kappa B activation. Conclusions-These findings suggest that LIGHT could serve as a molecular link between lipid metabolism, inflammation, and thrombus formation, which are all features of atherosclerotic plaques.

【 授权许可】

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