Effects of miR-155 on hypertensive rats via regulating vascular mesangial hyperplasia

Objective:Vascular smooth muscle cell (VSMC) excessive proliferation is related to hypertension. The cell cycle inhibitory factor (p27) can arrest cell cycle, while its down-regulation is associated with hypertension. It is found that microRNA-155 (miR-155) plays a regulatory role in VSMC proliferation, while its relationship with hypertension is still unclear. Bioinformatics analysis reveals the targeted relationship between miR-155 and the 3'-UTR of p27 mRNA. This study aims to explore the role of miR-155 in regulating p27 expression, VSMC proliferation and apoptosis, and the pathogenesis of hypertension.

Materials and methods:Dual luciferase reporter gene assay confirmed the relationship between miR-155 and p27. MiR-155, p27, α-smooth muscle actin (α-SMA), and Ki-67 expressions in the thoracic aorta media of rat hypertension model were detected. VSMCs were cultured in vitro and divided into five groups, including anti-miR-NC, anti-miR-155, pIRES2-blank, pIRES2-p27, and anti-miR-155 + pIRES2-p27 groups. Cell cycle was evaluated by using flow cytometry. Cell proliferation was detected with EdU staining. Hypertension rats were randomly divided into antagomir-155 and antagomir-control. Caudal artery systolic and diastolic pressures were measured.

Results:MiR-155 targeted suppressed p27 expression. MiR-155 and Ki-67 expressions significantly enhanced, while p27 and α-SMA levels reduced in the tunica media from hypertension rats compared with control. Down-regulation of miR-155 and/or up-regulation of p27significantly declined cell proliferation and arrested cell cycle in G1 phase. Antagomir-155 injection markedly decreased systolic and diastolic pressures, elevated p27 and α-SMA expressions in media, and reduced the thickness of tunica media.

Conclusions:MiR-155 promoted VSMC proliferation by targeting p27. MiR-155 enhancement was related to hypertension. MiR-155 played a therapeutic effect on hypertension.

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