Monocyte subpopulation profiling indicates CDK6-derived cell differentiation and identifies subpopulation-specific miRNA expression sets in acute and stable coronary artery disease [Profiling von Monozyten-Subpopulationen zeigt CDK6-abgeleitete Zelldifferenzierung an und identifiziert subpopulationsspezifische miRNA-Expressionssätze bei akuter und stabiler koronarer Herzkrankheit]

Witten, Anika; Martens, Leonie; Schaefer, Ann-Christin; Troidl, Christian; Pankuweit, Sabine; Vlacil, Ann-Kathrin; Oberoi, Raghav; Schieffer, Bernhard; Grote, Karsten; Stoll, Monika; Markus, Birgit

Abstract

Coronary artery disease (CAD) is a long-lasting infammatory disease characterized by monocyte migration into the vessel wall leading to clinical events like myocardial infarction (MI). However, the role of monocyte subsets, especially their miRNA-driven diferentiation in this scenario is still in its infancy. Here, we characterized monocyte subsets in controls and disease phenotypes of CAD and MI patients using fow cytometry and miRNA and mRNA expression profling using RNA sequencing. We observed major diferences in the miRNA profles between the classical (CD14++CD16− ) and nonclassical (CD14+ CD16++) monocyte subsets irrespective of the disease phenotype suggesting the Cyclin-dependent Kinase 6 (CDK6) to be an important player in monocyte maturation. Between control and MI patients, we found a set of miRNAs to be diferentially expressed in the nonclassical monocytes and targeting CCND2 (Cyclin D2) that is able to enhance myocardial repair. Interestingly, miRNAs as miR-125b playing a role in vascular calcifcation were diferentially expressed in the classical subset in patients sufering from CAD and not MI in comparison to control samples. In conclusion, our study describes specifc peculiarities of monocyte subset miRNA expression in control and diseased samples and provides basis to further functional analysis and to identify new cardiovascular disease treatment targets.