MiR-193-3p suppresses phenotypic switching in vascular smooth muscle cells by regulating IGF2 during in-stent restenosis.

Abstract

Background: Dysregulated proliferation and migration of vascular smooth muscle cells (VSMCs) are central to the development of in-stent restenosis (ISR). Clinically, regulating VSMC phenotype during proliferation and migration presents a potential therapeutic approach to prevent IRS. However, the role of miR-193-3p in ISR pathogenesis remains largely uncharacterized.

Objective: To investigate the role of miR-193-3p in ISR pathogenesis, focusing on the molecular mechanisms mediated by miR-193-3p, specifically the miR-193-3p/insulin-like growth factor-2 (IGF2) axis in regulating ISR.

Methods: Serum levels of miR-193-3p were quantified in ISR patients and healthy controls using quantitative real-time polymerase chain reaction (qPCR). miR-193-3p mimic transfection in VSMCs was confirmed by qPCR. The phenotypic switching of VSMCs was assessed via qPCR and western blot. Proliferative and migratory activities were evaluated using CCK-8 and Transwell assays, respectively. IGF2 levels in VSMCs were assessed using qPCR and WB assays.

Results: Serum levels of miR-193-3p were significantly reduced in ISR patients compared to healthy controls (P < 0.05). Overexpressing miR-193-3p markedly suppressed VSMC proliferation and migration (P < 0.05), while upregulating differentiation-associated VSMC markers at both mRNA and protein levels (P < 0.05). Mechanistically, IGF2 was identified as a direct target of miR-193-3p. Additionally, miR-193-3p expression was elevated in VSMCs following IGF2 stimulation (P < 0.05), and this upregulation counteracted IGF2-induced proliferative and migratory activity (P < 0.05).

Conclusions: These findings suggest the miR-193-3p may serve as a potential biomarker for ISR and that targeting the miR-193-3p/IGF2 axis could be a promising strategy for managing ISR.