Exosome-mediated effects of BRCA1 on cardiovascular artery disease

Hairui Yu1, Dong Wei1, Weiqian Liao2

  • 1Department of Preventive Medicine, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen, 518000, China.

PubMed

Insights

BRCA1 in exosomes from M1 macrophages promotes coronary artery disease (CAD) by inducing cardiomyocyte apoptosis and affecting smooth muscle cells. This highlights a novel target for CAD treatment strategies.

Area of Science:

  • Cardiovascular Biology
  • Cellular and Molecular Medicine
  • Immunology

Background:

  • Coronary artery disease (CAD) atherosclerosis progression involves cardiomyocyte apoptosis and inflammation.
  • Macrophage-cardiomyocyte communication is significant in CAD patients.
  • BRCA1 is identified as a key apoptosis-related gene in CAD.

Purpose of the Study:

  • To investigate the role of BRCA1 in M1 macrophage-derived exosomes (Exo) in CAD progression.
  • To elucidate the mechanisms by which BRCA1-Exo influence cardiomyocyte and smooth muscle cell behavior.
  • To identify potential therapeutic targets for CAD.

Main Methods:

  • Single-cell RNA-seq analysis to identify cell communication and key genes.
  • Differential gene expression and WGCNA to pinpoint BRCA1.
  • In vitro experiments with BRCA1-transfected M1 macrophages, isolated Exo, cardiomyocytes, and smooth muscle cells.
  • In vivo studies to assess CAD progression.

Main Results:

  • BRCA1-Exo from M1 macrophages induce cardiomyocyte apoptosis.
  • BRCA1-Exo alter smooth muscle cell behavior.
  • In vivo studies confirm BRCA1-Exo exacerbate CAD progression.
  • Significant macrophage-cardiomyocyte communication observed in CAD.

Conclusions:

  • Exosomes carrying BRCA1 from M1 macrophages contribute to CAD atherosclerosis progression.
  • BRCA1-Exo induce cardiomyocyte apoptosis and regulate smooth muscle cell behavior.
  • These findings suggest novel molecular targets for CAD treatment.

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