Potential Target miR-455 Delaying Arterial Stenosis Progression Through PTEN

Abstract

Background: Vascular smooth muscle cells (VSMC) underwent phenotypic switching upon stimulation signals, and this is the prerequisite for their proliferation and migration. Previous work revealed that miR-455 may be involved in vascular stenosis. Thus, this study aimed to explore potential targets and mechanisms underlying the dynamics of miR-455 in vascular stenosis.Methods: miR-455 and PTEN expression levels were studied in normal and stenosis tissue, as well as in VSMC in proliferation model. Manipulating miR-455 expression levels was achieved by transfection of either miR-455 mimic or inhibitor, and its effect on cell proliferation was studied by CCK-8 assay. Its effect on gene expression was studied by RT-qPCR and western blot. The expression regulation mechanism was studied by luciferase reporter system. Finally, the effect of miR-455 on regulating vascular stenosis was studied using a rat balloon-injured carotid artery stenosis model.Results: High expression levels of miR-455 were detected in both stenosis arterial tissues and VSMC proliferation models. In contrast, the expression levels of PTEN were downregulated in these systems. miR-455 transfected VSMC showed higher levels of proliferation and decreased levels of PTEN. Potential binding sites between miR-455 and PTEN 3′UTR were predicted and confirmed. NF-kB p65 was found to bind directly on miR-455 promoter region and regulate its transcription. The progression of arterial stenosis could be delayed by introducing miR-455 antagomir.Conclusions: The p65/miR-455/PTEN signaling pathway plays a crucial role in regulating VSMC proliferation and vascular stenosis. This indicated that miR-455 is a novel target that would help improve treatment outcomes in patients suffering from vascular stenosis.

Vascular smooth muscle cells in intimal hyperplasia, an update

“…Non-coding RNAs also regulate VSMC apoptosis and survival pathways. Several miRNAs regulate PTEN expression in VSMCs, thereby influencing the PI3K/Akt/mTOR pathway (miR-26a, miR-21), cell proliferation and survival ( Horita et al, 2011 ; Lin et al, 2021 ). Non-coding RNAs also regulate caspase activation, either through Bcl2-mediated regulation (miR-21, HIF1α-AS1), or through the tumor suppressor p53 (Linc-p21, circ-ANRIL, H19).…”

Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

“…PTEN is a negative regulator of the PI3K/AKT signalling pathway. PTEN activators can attenuate intimal hyperplasia formation in injured vessels [98] , prevent phenotypic switching in vSMCs as well as inhibiting proliferation and migration of SMCs and cancer cells [99] . Though no studies have reported the activity of seaweed on PTEN in vSMCs, a handful of studies have reported its activity in upregulating PTEN expression in cancer cells [100] .…”

Dipsacoside B Inhibits the Migration and Proliferation of VSMCs and Blunts Neointimal Formation by Upregulating PTEN Expression

“…Increasing evidence [8,11,24] showed that PTEN was a potent regulator in inhibiting the proliferation and migration of VSMCs. To determine whether PTEN was involved in the activity of DB, we employed western blot and immunohistochemistry to measure the expression of PTEN in vivo.…”

“…Therefore, targeting hyper proliferating VSMCs and suppressing VSMCs' phenotype switch can contribute to therapeutic outcome in vascular diseases [7]. Multiple studies [8,9] have demonstrated that phosphatase and tension homolog deleted on chromosome 10 (PTEN) is the key regulator in VSMCs' phenotype switch and sequentially alters behaviors in the migration and proliferation of VSMC. Downregulation of PTEN promotes the migration and proliferation of VSMCs [10], whereas upregulation of PTEN suppresses the migration and proliferation of VSMCs, blunts neointimal formation, and alleviate stenosis [9,11,12].…”