Substantial dysregulation of miRNA passenger strands underlies the vascular response to injury

Abstract

Vascular smooth muscle cell (VSMC) dedifferentiation is a common feature of vascular disorders leading to pro-migratory and proliferative phenotypes, a process induced through growth factor and cytokine signaling cascades. Recently, many studies have demonstrated that small non-coding RNAs (miRNAs) can induce phenotypic effects on VSMCs in response to vessel injury. However, most studies have focused on the contribution of individual miRNAs. Our study aimed to conduct a detailed and unbiased analysis of both guide and passenger miRNA expression in vascular cells in vitro and disease models in vivo. We analyzed 100 miRNA stem loops by TaqMan Low Density Array (TLDA) from primary VSMCs in vitro. Intriguingly, we found that a larger proportion of the passenger strands was significantly dysregulated compared to the guide strands after exposure to pathological stimuli, such as platelet-derived growth factor (PDGF) and IL-1α. Similar findings were observed in response to injury in porcine vein grafts and stent models in vivo. In these studies, we reveal that the miRNA passenger strands are predominantly dysregulated in response to vascular injury.