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.
Highlights
MicroRNAs are a class of non-coding RNAs known to play a prominent role in gene regulation at a post-transcriptional level [1,2,3]
Human Vascular smooth muscle cell (VSMC) were treated with platelet-derived growth factor (PDGF), interleukin 1α (IL-1α) or a combination of both to mimic a number of the pathologic signals induced by vascular injury
PDGF induced a significant increase in VSMC migration (Figure S2A), and the pro-proliferative phenotype was confirmed by a reduction in the expression of the cyclin-dependent kinase inhibitor 1B (CDKN1B)
Summary
MicroRNAs (miRNAs) are a class of non-coding RNAs known to play a prominent role in gene regulation at a post-transcriptional level [1,2,3]. Duplex [4], which, on processing, generates two single-stranded RNA molecules. MiRNAs are loaded onto Argonaute to produce a RNA-induced silencing complex (RISC), which exerts translational repression via an imperfect binding to the mRNA target, generally localized in the 30 UTR. An equal amount of the two strands from the miRNA:miRNA * duplex is produced by the transcription but their accumulation becomes asymmetric [5]. The mature sequences of the two strand forms can regulate distinct sets of mRNA transcripts or common targets through different hybridization sites on the mRNA targeted
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