The accumulation of senescent cells in the vasculature over the lifespan contributes to vascular remodeling due to the severely impaired functional properties of the cells. Micro RNAs (miRs) are promising therapeutical targets as they exhibit diverse and cell-specific functions and can be effectively targeted in vivo. Targeting miR-127-3p might be an attractive approach to enhance vascular healing and regeneration in a cell-specific manner, thereby limiting angioplasty-related complications.

MiR-127-3p expression levels in different human cell types and mice tissue are addressed utilizing qPCR. The initial screenings revealed miR-127-3p as a highly regulated miR in restenosis and aged (20 months) C57BL/6 mice. Additionally, replicative senescent human vascular smooth muscle cells (HVSMC) and human coronary artery endothelial cells (HCAEC) showed an enhanced expression of miR-127-3p (p<0.05) compared to non-senescent cells. Functional effects of miR-127-3p on HVSMCs and HCAECs are assessed via transfection with either pre-miR or antagomir followed by different in vitro assays. Overexpression of miR-127-3p in vitro reduced HVSMC proliferation (p<0.05) and migrational (p<0.05) capacity. Regulated target genes were identified via in silico analysis. Target gene regulation after transfection was shown in VSMCs on the mRNA level utilizing qPCR. The regulation was also confirmed on the protein level via western blot analysis.

This study has identified miR-127-3p as a contributing factor in HVSMC function during the development of cellular senescence and might therewith be a modulating factor in vascular remodeling. Further studies need to be carried out to validate the potential of miR-127-3p as a therapeutic target in cardiovascular aging and diseases.