MicroRNA-146a Induces Lineage-Negative Bone Marrow Cell Apoptosis and Senescence by Targeting Polo-Like Kinase 2 Expression.

Objective—Lineage-negative bone marrow cells (lin− BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin− BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin− BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin− BMCs is a critical step in understanding the process of vascular repair. The aim of this study was to characterize the role of the miR-146a–Polo-like kinase 2 (Plk2) network in regulating lin− BMC senescence, apoptosis, and their angiogenic capability. Approach and Results—Transcriptome analysis in lin− BMCs isolated from young and aged wild-type and ApoE−/− (apolipoprotein E) mice showed a significant age-associated increase in miR-146a expression. In silico analysis, expression study and Lucifera...