The persistence of low-grade inflammatory monocytes contributes to aggravated Atherosclerosis
dc.contributor.author | Geng, Shuo | en |
dc.contributor.author | Chen, Keqiang | en |
dc.contributor.author | Yuan, Ruoxi | en |
dc.contributor.author | Maitra, Urmila | en |
dc.contributor.author | Na, Diao | en |
dc.contributor.author | Chen, Chun | en |
dc.contributor.author | Zhang, Yao | en |
dc.contributor.author | Li, Liwu | en |
dc.contributor.author | Xiong, Huabao | en |
dc.contributor.author | Peng, Liang | en |
dc.contributor.author | Hu, Yuan | en |
dc.contributor.author | Qi, Chen-Feng | en |
dc.contributor.author | Pierce, Susan | en |
dc.contributor.author | Ling, Wenhua | en |
dc.contributor.department | Biological Sciences | en |
dc.date.accessioned | 2017-11-13T19:43:18Z | en |
dc.date.available | 2017-11-13T19:43:18Z | en |
dc.date.issued | 2016-11-08 | en |
dc.description.abstract | Sustained 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.sponsorship | This 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.mimetype | application/pdf | en |
dc.identifier.doi | https://doi.org/10.1038/ncomms13436 | en |
dc.identifier.uri | http://hdl.handle.net/10919/80354 | en |
dc.identifier.volume | 7 | en |
dc.language.iso | en | en |
dc.publisher | Nature | en |
dc.rights | In Copyright | en |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | en |
dc.title | The persistence of low-grade inflammatory monocytes contributes to aggravated Atherosclerosis | en |
dc.title.serial | Nature Communications | en |
dc.type | Article - Refereed | en |
dc.type.dcmitype | Text | en |
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