Identification of miR136, miR155, and miR183 in Vascular Calcification in Human Peripheral Arteries.

Vascular calcification (V) is an independent risk factor for all-cause and cardiovascular mortality. Vascular smooth muscle cells (VSMCs) play a major role in VC as they can acquire mineralizing properties when exposed to osteogenic conditions. Despite its clinical impact, there are still no dedicated therapeutic strategies targeting VC. To address this issue, we used human calcified and non-calcified atherosclerotic arteries (ECLAGEN Biocollection) to screen and identify microRNA (miR) associated with VC. We combined non-biased miRNomic (microfluidic arrays) and transcriptomic analysis to select miR candidates and their putative target genes with expression associated with VC and ossification. We further validated miR functional regulation and function in relation to cell mineralization using primary human VSMCs. Our study identified 12 miRs associated with VC in carotid and femoral arteries. Among those, we showed that miR136, miR155, and miR183 expression were regulated during VSMC mineralization and that overexpression of these miRs promoted VSMC mineralization. Cross-analysis of this miRNomic and a transcriptomic analysis led to the identification of CD73 and Smad3 pathways as putative target genes responsible for mediating the miR155 pro-mineralizing function. These results highlight the potential benefit of miR155 inhibition in limiting VC development in peripheral atherosclerotic arteries.