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

Dyslipidemia is associated with a low-grade inflammatory process modified by the immune response, mainly monocytes and macrophages. Metabolically activated macrophages (characterized by the expression of CD36, ABCA1 and PLIN2 receptors, and by exhibit trimethylation of the lysine 4 and 27 of the histone 3) have been implicated in obesity and dyslipidemia. However, it has not been reported a population of circulating monocytes with the same phenotype. We hypothesized that continuous exposure to low-density lipoproteins (LDL-c) induces epigenetic changes in monocytes, leading to their polarization into metabolically activated macrophages. We investigated the phenotypic expression of circulating monocyte and macrophage subsets in 23 individuals living with LDL-c dyslipidemia. Using dimensionality reduction and clustering algorithms within a comprehensive analytical model, we analyzed flow cytometry data to evaluate epigenetic changes, specifically H3K4me3 and H3K27me3, in clustered subsets. This model allowed us to identify two statistically significant phenotypes of metabolically activated monocytes that were more prevalent in dyslipidemia patients than in controls, exhibiting distinct expression levels of trimethylation of the lysine 4 and 27 of the histone 3. This approach allowed us to delineate different monocyte and macrophages associated to the metabolically activated phenotype in dyslipidemia.