Monocyte subpopulation profiling indicates CDK6-derived cell differentiation and identifies subpopulation-specific

Anika Witten1,2, Leonie Martens1, Ann-Christin Schäfer3

  • 1Genetic Epidemiology, Institute for Human Genetics, Westfälische Wilhelms-University, Domagkstraße 3, 48149, Münster, Germany.

Scientific Reports
|April 5, 2022
PubMed

Insights

Investigating coronary artery disease (CAD) and myocardial infarction (MI) patients, this study reveals distinct microRNA (miRNA) profiles in monocyte subsets, offering new cardiovascular disease treatment targets.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Molecular Biology

Background:

  • Coronary artery disease (CAD) is a chronic inflammatory condition involving monocyte infiltration of the vessel wall, potentially leading to myocardial infarction (MI).
  • The specific roles of distinct monocyte subsets and their microRNA (miRNA)-driven differentiation in CAD pathogenesis remain largely unexplored.

Purpose of the Study:

  • To characterize and compare miRNA expression profiles in classical and nonclassical monocyte subsets from healthy controls and patients with CAD and MI.
  • To identify novel miRNA-mRNA interactions and potential therapeutic targets for cardiovascular diseases.

Main Methods:

  • Flow cytometry was used to identify and isolate monocyte subsets (classical: CD14++CD16-, nonclassical: CD14+CD16++).
  • RNA sequencing was employed for comprehensive miRNA and mRNA expression profiling in isolated monocyte subsets.
  • Bioinformatic analysis was performed to identify differentially expressed miRNAs and their potential gene targets.

Main Results:

  • Significant differences in miRNA profiles were observed between classical and nonclassical monocyte subsets, independent of disease status, highlighting Cyclin-dependent Kinase 6 (CDK6) in monocyte maturation.
  • Nonclassical monocytes from MI patients showed differential expression of miRNAs targeting CCND2 (Cyclin D2), a gene potentially involved in myocardial repair.
  • Specific miRNAs, including miR-125b associated with vascular calcification, were differentially expressed in classical monocytes of CAD patients compared to controls.

Conclusions:

  • This study elucidates unique miRNA expression patterns within monocyte subsets in cardiovascular disease states.
  • The findings provide a foundation for further functional investigations into monocyte subsets and their miRNAs.
  • Identified miRNA-mRNA interactions represent potential novel therapeutic targets for treating cardiovascular diseases like CAD and MI.

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