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Myeloid CD40 defici...
Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages’ transition into a pro-inflammatory state
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- Bosmans, Laura A. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- van Tiel, Claudia M. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Aarts, Suzanne A.B.M. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Willemsen, Lisa (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Baardman, Jeroen (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- van Os, Bram W. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- den Toom, Myrthe (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Beckers, Linda (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Ahern, David J. (författare)
- Kennedy Institute of Rheumatology
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- Levels, Johannes H.M. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Jongejan, Aldo (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Moerland, Perry D. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Verberk, Sanne G.S. (författare)
- Vrije Universiteit Amsterdam
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- van den Bossche, Jan (författare)
- Vrije Universiteit Amsterdam,Academic Medical Center of University of Amsterdam (AMC)
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- de Winther, Menno M.P.J. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Weber, Christian (författare)
- Munich Cluster for Systems Neurology,German Centre for Cardiovascular Research,Maastricht University Medical Centre,University Hospital Munich
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- Atzler, Dorothee (författare)
- Munich Cluster for Systems Neurology,Ludwig-Maximilian University of Munich,University Hospital Munich
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- Monaco, Claudia (författare)
- Kennedy Institute of Rheumatology
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- Gerdes, Norbert (författare)
- University Hospital of Düsseldorf
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- Shami, Annelie (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Academic Medical Center of University of Amsterdam (AMC)
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- Lutgens, Esther (författare)
- Academic Medical Center of University of Amsterdam (AMC),Mayo Clinic Minnesota,German Centre for Cardiovascular Research,Ludwig-Maximilian University of Munich
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(creator_code:org_t)
- 2022-05-19
- 2023
- Engelska 15 s.
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:5, s. 1146-1160
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. Method and Cd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe−/− background were generated (CD40wt and CD40mac−/− , respect-Results ively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac−/− compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac−/− atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b− macrophages in the atherosclerotic aorta of CD40mac−/− compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac−/− mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1). Conclusions We here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- Atherosclerosis
- CD40
- Inflammation
- Macrophage
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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- Av författaren/redakt...
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Bosmans, Laura A ...
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van Tiel, Claudi ...
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Aarts, Suzanne A ...
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Willemsen, Lisa
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Baardman, Jeroen
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van Os, Bram W.
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visa fler...
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den Toom, Myrthe
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Beckers, Linda
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Ahern, David J.
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Levels, Johannes ...
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Jongejan, Aldo
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Moerland, Perry ...
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Verberk, Sanne G ...
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van den Bossche, ...
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de Winther, Menn ...
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Weber, Christian
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Atzler, Dorothee
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Monaco, Claudia
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Gerdes, Norbert
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Shami, Annelie
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Lutgens, Esther
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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Cardiovascular R ...
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Lunds universitet