Zysset, Daniel; Weber, Benjamin; Rihs, Silvia; Brasseit, Jennifer; Freigang, Stefan Bernd; Riether, Carsten; Banz Wälti, Yara; Cerwenka, Adelheid; Simillion, Cedric; Marques-Vidal, Pedro; Ochsenbein, Adrian; Saurer, Leslie; Müller, Christoph (2016). TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis. Nature communications, 7(13151), p. 13151. Nature Publishing Group 10.1038/ncomms13151
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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.
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