TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis
| Autor: | Adelheid Cerwenka, Carsten Riether, Pedro Marques-Vidal, Cedric Simillion, Christoph Mueller, Jennifer Brasseit, Adrian F. Ochsenbein, Yara Banz, Silvia Rihs, Daniel Zysset, Benjamin Weber, Stefan Freigang, Leslie Saurer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myeloid medicine.medical_treatment General Physics and Astronomy Monocytes Mice 0302 clinical medicine Antigens Ly Aorta Foam cell Mice Knockout Multidisciplinary Cell Differentiation 3. Good health medicine.anatomical_structure Cytokine Cholesterol Monocyte differentiation Cytokines Female medicine.symptom Science Inflammation 610 Medicine & health Biology Diet High-Fat General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Apolipoproteins E Monocytosis medicine Animals Humans Dyslipidemias Innate immune system Monocyte General Chemistry medicine.disease Atherosclerosis Lipid Metabolism Triggering Receptor Expressed on Myeloid Cells-1 Mice Inbred C57BL Disease Models Animal 030104 developmental biology Gene Expression Regulation Immunology 570 Life sciences biology 030215 immunology Foam Cells |
| Zdroj: | 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 Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-16 (2016) Nature communications, vol. 7, pp. 13151 |
| Popis: | 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. TREM-1 is a receptor that amplifies acute pro-inflammatory responses in infection. Here the authors show that TREM-1 plays an important role in atherosclerosis, a chronic and non-infectious disease, by critically skewing myelopoiesis towards preferential monocyte differentiation and by contributing to CD36-driven cellular lipid accumulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|