| First Author | Zysset D | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13151 | PubMed ID | 27762264 |
| Mgi Jnum | J:242597 | Mgi Id | MGI:5905707 |
| Doi | 10.1038/ncomms13151 | Citation | Zysset D, et al. (2016) TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis. Nat Commun 7:13151 |
| abstractText | Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune responses, but its significance in non-infectious diseases remains unclear. Here, we demonstrate that TREM-1 promotes cardiovascular disease by exacerbating atherosclerosis. TREM-1 is expressed in advanced human atheromas and is highly upregulated under dyslipidemic conditions on circulating and on lesion-infiltrating myeloid cells in the Apoe-/- mouse model. TREM-1 strongly contributes to high-fat, high-cholesterol diet (HFCD)-induced monocytosis and synergizes with HFCD serum-derived factors to promote pro-inflammatory cytokine responses and foam cell formation of human monocyte/macrophages. Trem1-/-Apoe-/- mice exhibit substantially attenuated diet-induced atherogenesis. In particular, our results identify skewed monocyte differentiation and enhanced lipid accumulation as novel mechanisms through which TREM-1 can promote atherosclerosis. Collectively, our findings illustrate that dyslipidemia induces TREM-1 surface expression on myeloid cells and subsequently synergizes with TREM-1 to enhance monopoiesis, pro-atherogenic cytokine production and foam cell formation. |
