| First Author | Geng S | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13436 | PubMed ID | 27824038 |
| Mgi Jnum | J:242723 | Mgi Id | MGI:5906099 |
| Doi | 10.1038/ncomms13436 | Citation | Geng S, et al. (2016) The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis. Nat Commun 7:13436 |
| abstractText | 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. |
