TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis.

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Zysset, Daniel; Weber, Benjamin; Rihs, Silvia; Brasseit, Jennifer; Freigang, Stefan Bernd; Riether, Carsten; Banz Wälti, Yara; Ochsenbein, Adrian; Saurer, Leslie and Müller, Christoph

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Christa Hagert

Date Deposited:

21 Dec 2016 14:49

Last Modified:

24 Apr 2017 14:34

Publisher DOI:

10.1038/ncomms13151

PubMed ID:

27762264

BORIS DOI:

10.7892/boris.92033

URI:

https://boris.unibe.ch/id/eprint/92033

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