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"Faces" of the day:

Katharina Jandl

Nina Höller

Nariae Baik-Schneditz

Ellen Heitzer

Marianne Brodmann

Ewald Kolesnik

Bernhard Schwaberger

Maximilian Seles

Gabor Toth-Gayor

Lukas Peter Mileder

Niels Hammer

Christian Josef Hill

Christian Viertler

Philipp Klaritsch

Daniel Scherr

Harald Köfeler

Gerhard Pichler

Roland Malli

Michael Fuchsjäger

Gernot Plank

Peter Fickert

Richard Zigeuner

Peter Holzer

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Leipner, J; Dederichs, TS; von, Ehr, A; Rauterberg, S; Ehlert, C; Merz, J; Dufner, B; Hoppe, N; Krebs, K; Heidt, T; von, Zur, Muehlen, C; Stachon, P; Ley, K; Wolf, D; Zirlik, A; Bode, C; Hilgendorf, I; Härdtner, C.
Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe^-/- mice.
Mol Metab. 2021; 53:101250 Doi: 10.1016/j.molmet.2021.101250 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Zirlik Andreas

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Abstract:

OBJECTIVE: Interferon regulatory factor (IRF) 5 is a transcription factor known for promoting M1 type macrophage polarization in vitro. Given the central role of inflammatory macrophages in promoting atherosclerotic plaque progression, we hypothesize that myeloid cell-specific deletion of IRF5 is protective against atherosclerosis. METHODS: Female Apoe^-/-Lysm^Cre/+Irf5^fl/fl and Apoe^-/-Irf5^fl/fl mice were fed a high-cholesterol diet for three months. Atherosclerotic plaque size and compositions as well as inflammatory gene expression were analyzed. Mechanistically, IRF5-dependent bone marrow-derived macrophage cytokine profiles were tested under M1 and M2 polarizing conditions. Mixed bone marrow chimeras were generated to determine intrinsic IRF5-dependent effects on macrophage accumulation in atherosclerotic plaques. RESULTS: Myeloid cell-specific Irf5 deficiency blunted LPS/IFNγ-induced inflammatory gene expression in vitro and in the atherosclerotic aorta in vivo. While atherosclerotic lesion size was not reduced in myeloid cell-specific Irf5-deficient Apoe^-/- mice, plaque composition was favorably altered, resembling a stable plaque phenotype with reduced macrophage and lipid contents, reduced inflammatory gene expression and increased collagen deposition alongside elevated Mertk and Tgfβ expression. Irf5-deficient macrophages, when directly competing with wild type macrophages in the same mouse, were less prone to accumulate in atherosclerotic lesion, independent of monocyte recruitment. Irf5-deficient monocytes, when exposed to oxidized low density lipoprotein, were less likely to differentiate into macrophage foam cells, and Irf5-deficient macrophages proliferated less in the plaque. CONCLUSION: Our study provides genetic evidence that selectively altering macrophage polarization induces a stable plaque phenotype in mice.

Find related publications in this database (Keywords)

Atherosclerosis

Interferon regulatory factor 5

Macrophage polarization (M1, M2)

Plaque stabilization

Anti-inflammation

Aortic macrophages

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