Comprehensive Lipid Profiling Recapitulates Enhanced Lipolysis and Fatty Acid Metabolism in Intimal Foamy Macrophages

Jae Won Seo1, Kyu Seong Park2, Gwang Bin Lee1

  • 1Department of Chemistry, Yonsei University, Seoul 03722, Korea.

Immune Network
|September 6, 2023
PubMed

Insights

Foamy macrophages in atherosclerosis exhibit distinct lipid profiles, with altered levels of various lipids and changes in genes regulating lipid synthesis and breakdown. This lipidomic analysis provides crucial insights into macrophage phenotypes in atherosclerotic lesions.

Area of Science:

  • Cardiovascular Biology
  • Macrophage Biology
  • Lipid Metabolism

Background:

  • Lipid accumulation in macrophages is a hallmark of atherosclerosis.
  • Foamy macrophages (FM) in atherosclerotic lesions display altered inflammatory gene expression compared to non-foamy macrophages (NFM).
  • Understanding macrophage lipid metabolism is key to elucidating their phenotypic changes in atherosclerosis.

Purpose of the Study:

  • To perform direct lipid profiling of primary aortic macrophages from atherosclerotic aortas.
  • To comprehensively analyze the lipid profiles of intimal foamy macrophages (FM), intimal non-foamy macrophages (NFM), and adventitial macrophages.
  • To correlate lipidomic data with gene expression related to lipid metabolism in these distinct macrophage populations.

Main Methods:

  • Utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) for comprehensive lipidomic analysis.
  • Isolated and analyzed primary intimal foamy macrophages (FM), intimal non-foamy macrophages (NFM), and adventitial macrophages from Ldlr-/- mouse aortas.
  • Performed gene expression analysis for key enzymes involved in lipid metabolism pathways.

Main Results:

  • Foamy macrophages (FM) showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin.
  • Decreased levels of phosphatidylethanolamine, phosphatidic acid, ceramide, and notably triacylglycerol (TG) were observed in FM compared to NFM.
  • Gene expression analysis revealed increased lipolysis-related genes (Pnpla2, Lpl) and decreased TG synthesis genes (Lpin2, Dgat1) in FM.

Conclusions:

  • Direct lipidomic profiling reveals significant differences in lipid composition between foamy and non-foamy macrophages in the atherosclerotic aorta.
  • Alterations in lipid metabolism pathways, including enhanced lipolysis and reduced triacylglycerol synthesis, characterize foamy macrophages.
  • These findings clarify the lipid-driven phenotypes of macrophages within atherosclerotic lesions, offering potential therapeutic targets.

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