Stretch‐sensitive microRNA expression and signaling events in vascular smooth muscle

Abstract

Vascular smooth muscle cells are constantly exposed to mechanical force by the blood pressure, which is thought to regulate smooth muscle growth, differentiation and contractile function. We have previously shown that expression of small non‐coding RNAs, microRNAs (miRNAs), is essential for regulation of smooth muscle phenotype including stretch‐dependent contractile differentiation.In this study we have investigated the effect of mechanical stretch on miRNA expression and the role of stretch‐sensitive miRNAs for intracellular signaling in smooth muscle.Mechanical stretch was applied to mouse portal veins in organ culture ex vivo by attaching a gold weight at one end of the vessel for 24h. MiScript whole genome miRNA PCR arrays analysis, comparing miRNA levels in stretched versus non‐stretched portal veins, revealed a dramatic decrease in the miR‐144/451 cluster level with no change in other active miRNA strands. Furthermore, we could confirm that these miRNAs target the AMPK signaling pathway, which correlates with an increased AMPK activation in stretched portal veins.In conclusion, our results suggest that reduced expression of miR‐144/451 in stretched portal veins could participate in the regulation of AMPK signaling. This effect may represent a negative feedback mechanism, limiting stretch‐induced growth in vascular smooth muscle.