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Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPARγ signature

  • 0Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
European Heart Journal +

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September 19, 2019

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September 19, 2019

View abstract on PubMed

Summary

This summary is machine-generated.

Nuclear receptor corepressor 1 (NCOR1) deficiency in macrophages worsens atherosclerosis by promoting foam cell formation and inflammation. Stabilizing NCOR1-PPARγ binding may offer a therapeutic strategy for atherosclerosis patients.

Area Of Science

  • Cardiovascular Biology
  • Molecular Endocrinology
  • Immunometabolism

Background

  • Nuclear receptors and cofactors are crucial in atherosclerosis.
  • Nuclear receptor corepressors (NCOR) regulate nuclear receptor activity.
  • NCOR1 deletion in macrophages increases atherosclerotic molecules, but its role in atherogenesis is unclear.

Purpose Of The Study

  • To investigate the role of macrophage NCOR1 in atherosclerosis development.
  • To elucidate the molecular mechanisms linking NCOR1 to atherogenesis.

Main Methods

  • Generated myeloid cell-specific Ncor1 knockout mice crossed with Ldlr knockout mice.
  • Analyzed atherosclerotic lesion development, foam cell formation, and gene expression in macrophages.
  • Investigated NCOR1's regulation of PPARγ target genes and CD36 scavenger receptor.

Main Results

  • Myeloid cell-specific Ncor1 deletion aggravated atherosclerosis in mice.
  • Macrophage Ncor1 deficiency increased foam cell formation, inflammation, necrotic cores, and reduced fibrous caps.
  • NCOR1 suppresses PPARγ target genes, reducing oxidized LDL uptake; human plaques show reduced NCOR1 and increased PPARγ signature.

Conclusions

  • Macrophage NCOR1 inhibits pro-atherogenic PPARγ functions in atherosclerosis.
  • Stabilizing NCOR1-PPARγ binding is a potential therapeutic strategy against atherosclerosis progression.

Keywords:

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