Chemokine Ligands and Receptors Regulate Macrophage Polarization in Atherosclerosis: A Comprehensive Database Mining

Wanqian Yu1, Linghua Fu1, Guangtao Lei1

  • 1Department of Cardiovascular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

CJC Open
|April 4, 2025
PubMed

Insights

Chemokines, regulated by transcription factors and microRNAs, influence macrophage polarization in atherosclerosis. Targeting these chemokines and macrophage polarization offers a potential treatment strategy for atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Bioinformatics

Background:

  • Atherosclerosis is a systemic cardiovascular disease where macrophages are central.
  • Current treatments for atherosclerosis are insufficient for complete reversal.
  • The role of chemokines in atherosclerosis mechanisms remains largely unknown.

Purpose of the Study:

  • To investigate the effects and mechanisms of chemokines in atherosclerosis using bioinformatics.
  • To identify key regulatory factors and pathways involved in chemokine-mediated macrophage polarization in atherosclerosis.

Main Methods:

  • Utilized public databases (NCBI-GEO, ArrayExpress, scRNA-seq) for chemokine data.
  • Analyzed chemokine expression in mouse tissues, atherosclerotic plaques, and during macrophage polarization using Metascape and GEO2R.
  • Employed Ingenuity Pathway Analysis (IPA) to identify upstream regulatory factors like transcription factors and microRNAs.

Main Results:

  • Chemokines in atherosclerosis are regulated by transcription factors and microRNAs.
  • STAT1, IRF7, and IRF1 regulate macrophage polarization (M1, M2, M2a, M2b) via specific chemokines (e.g., CCL4, CCL19, CCL5, CCR7).
  • Transcription factors can promote or inhibit atherosclerosis, while microRNAs only inhibit; CCL4 and CXCL3 show specific roles in macrophage polarization.

Conclusions:

  • Regulating chemokines and macrophage polarization presents a therapeutic avenue for atherosclerosis.
  • Specific chemokines including CCL4, CCL5, CCL8, CCL19, CXCL3, CXCL10, CXCL13, and CCR7 are implicated in atherosclerosis progression and regression.
Abstract