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Browsing by Author "Maitra, Urmila"

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    The persistence of low-grade inflammatory monocytes contributes to aggravated Atherosclerosis
    Geng, Shuo; Chen, Keqiang; Yuan, Ruoxi; Maitra, Urmila; Na, Diao; Chen, Chun; Zhang, Yao; Li, Liwu; Xiong, Huabao; Peng, Liang; Hu, Yuan; Qi, Chen-Feng; Pierce, Susan; Ling, Wenhua (Nature, 2016-11-08)
    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.