Down-regulation of mir-542-3p promotes neointimal formation in the aging rat.

Vascul Pharmacol

Department of Cardiology, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China. Electronic address:

Published: September 2015

Aim: To explore mir-542-3p mediated inhibition of vascular smooth muscle cell (VSMC) proliferation through the inhibition of Syk activation.

Methods And Results: MicroRNA (mir)-542-3p was selected for analysis based on miRNA microarray and qRT-PCR results. In vitro mir-542-3p expression was significantly downregulated in old (o)VSMCs compared with young (y)VSMCs under serum stimulation conditions. Upregulation of mir-542-3p in oVSMCs significantly inhibited VSMC proliferation, whereas downregulation of mir-542-3p in yVSMCs increased VSMC proliferation. We identified spleen tyrosine kinase (Syk) as a direct target of mir-542-3p by database search, and showed that its expression and phosphorylation were higher in oVSMCs than in yVSMCs after serum stimulation. Luciferase assays confirmed that Syk is a direct target of miR-3542-3p. Knock-down of mir-542-3p in yVSMCs inhibited the activation of the Syk downstream effectors STAT3 and STAT5, whereas mir-542-3p overexpression enhanced STAT3 and STAT5 activities. In a rat balloon injury model, mir-542-3p inhibited neointima formation and proliferating cell nuclear antigen (PCNA) protein expression.

Conclusion: Mir-542-3p modulates VSMC proliferation via the Syk/STAT3-STAT5 axis. Downregulation of mir-542-3p may explain age-related neointimal hyperplasia in rats.

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http://dx.doi.org/10.1016/j.vph.2015.05.010DOI Listing

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