Abstract
Calcium deposition in vascular smooth muscle cells (VSMCs) is a form of ectopic ossification in blood vessels. It can result in rigidity of the vasculature and an increase in cardiac events. Here, we report that the microRNA-134-5p ( miR-134-5p) potentiates inorganic phosphate (Pi)-induced calcium deposition in VSMCs by inhibiting histone deacetylase 5 (HDAC5). Using miRNA microarray analysis of Pi-treated rat VSMCs, we first selected miR-134-5p for further evaluation. Quantitative RT-PCR confirmed that miR-134-5p was increased in Pi-treated A10 cells, a rat VSMC line. Transfection of miR-134-5p mimic potentiated the Pi-induced increase in calcium contents. miR-134-5p increased the amounts of bone runt-related transcription factor 2 (RUNX2) protein and bone morphogenic protein (BMP2) mRNA in the presence of Pi but decreased the expression of osteoprotegerin (OPG). Bioinformatic analysis showed that the HDAC5 5’UTR was one of the targets of miR-134-5p . Hdac5 expression was downregulated by miR-134-5p mimic in an Hdac5 5’UTR-dependent manner. Overexpression of Hdac5 mitigated the calcium deposition induced by miR-134-5p . Our results suggest that a Pi-induced increase of miR-134-5p may cause vascular calcification through repression of HDAC5.
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