The persistence of low-grade inflammatory monocytes contributes to aggravated Atherosclerosis

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dc.contributor.authorGeng, Shuoen
dc.contributor.authorChen, Keqiangen
dc.contributor.authorYuan, Ruoxien
dc.contributor.authorMaitra, Urmilaen
dc.contributor.authorNa, Diaoen
dc.contributor.authorChen, Chunen
dc.contributor.authorZhang, Yaoen
dc.contributor.authorLi, Liwuen
dc.contributor.authorXiong, Huabaoen
dc.contributor.authorPeng, Liangen
dc.contributor.authorHu, Yuanen
dc.contributor.authorQi, Chen-Fengen
dc.contributor.authorPierce, Susanen
dc.contributor.authorLing, Wenhuaen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2017-11-13T19:43:18Zen
dc.date.available2017-11-13T19:43:18Zen
dc.date.issued2016-11-08en
dc.description.abstractSustained low-grade inflammation mediated by non-resolving inflammatory monocytes has long been suspected in the pathogenesis of atherosclerosis; however, the molecular mechanisms responsible for the sustainment of non-resolving inflammatory monocytes during atherosclerosis are poorly understood. Here we observe that subclinical endotoxemia, often seen in humans with chronic inflammation, aggravates murine atherosclerosis through programming monocytes into a non-resolving inflammatory state with elevated Ly6C, CCR5, MCP-1 and reduced SR-B1. The sustainment of inflammatory monocytes is due to the disruption of homeostatic tolerance through the elevation of miR-24 and reduction of the key negative-feedback regulator IRAK-M. miR-24 reduces the levels of Smad4 required for the expression of IRAK-M and also downregulates key lipid-processing molecule SR-B1. IRAK-M deficiency in turn leads to elevated miR-24 levels, sustains disruption of monocyte homeostasis and aggravates atherosclerosis. Our data define an integrated feedback circuit in monocytes and its disruption may lead to non-resolving low-grade inflammation conducive to atherosclerosis.en
dc.description.sponsorshipThis work was supported by the National Institute of Health grants R01 HL115835, R56AI108264 to L.L., RO1 AI104688 and R56AI091871 to H.X., and American Heart Association Award 15POST25860003 to S.G.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/ncomms13436en
dc.identifier.urihttp://hdl.handle.net/10919/80354en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherNatureen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.titleThe persistence of low-grade inflammatory monocytes contributes to aggravated Atherosclerosisen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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