Bioinformatic characterization and automated detection of metabolically activated monocyte subpopulations in...

Area of Science:

• Immunology
• Epigenetics
• Metabolic disease

Background:

• Dyslipidemia is linked to low-grade inflammation involving monocytes and macrophages.
• Metabolically activated macrophages, marked by specific receptors and histone trimethylation (H3K4me3, H3K27me3), are implicated in obesity and dyslipidemia.
• A circulating monocyte population with this activated phenotype had not been previously identified.

Purpose of the Study:

• To investigate if continuous exposure to low-density lipoprotein cholesterol (LDL-c) induces epigenetic changes in monocytes.
• To determine if these changes lead to monocyte polarization into metabolically activated macrophages.
• To identify and characterize circulating monocyte and macrophage subsets in individuals with LDL-c dyslipidemia.

Main Methods:

• Analysis of circulating monocyte and macrophage subsets in 23 individuals with LDL-c dyslipidemia.
• Utilized flow cytometry data analyzed with dimensionality reduction and clustering algorithms.
• Evaluated epigenetic modifications, specifically H3K4me3 and H3K27me3, in monocyte and macrophage subsets.

Main Results:

• Identified two statistically significant phenotypes of metabolically activated monocytes.
• These phenotypes were more prevalent in dyslipidemia patients compared to controls.
• The identified monocyte phenotypes exhibited distinct expression levels of H3K4me3 and H3K27me3.

Conclusions:

• Continuous LDL-c exposure may induce epigenetic changes in monocytes, promoting a metabolically activated phenotype.
• This study delineates specific monocyte and macrophage phenotypes associated with the metabolically activated state in dyslipidemia.
• The findings suggest a novel link between circulating monocytes, epigenetics, and dyslipidemia-associated inflammation.