Circ-Myh4_un770 Regulates VSMC Proliferation and Migration via miR-3593-5p in Vein Graft Stenosis: A Mechanism for Vascular Remodeling

IF 1.3 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiac Surgery Pub Date : 2025-09-26 DOI:10.1155/jocs/4874721

Baiqing Huang, Yirou Ma, Haiyang Wang, Wenli Wang, Xisheng Wang

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引用次数: 0

Abstract

Background: Coronary artery bypass grafting (CABG) is a cornerstone therapy for coronary heart disease (CHD), but vein graft failure (VGF) caused by neointimal hyperplasia remains a major clinical challenge. Vascular smooth muscle cell (VSMC) proliferation and migration are central to this pathology, yet the regulatory role of circular RNAs (circRNAs) in VGF remains unclear. This study aimed to identify circRNAs driving VSMC dysfunction and explore their mechanisms in vein graft stenosis.

Methods: A murine jugular vein-carotid artery bypass grafting model was established. RNA sequencing identified differentially expressed circRNAs in stenotic veins versus controls. Functional validation included circRNA knockdown/overexpression in VSMCs, proliferation (CCK-8, PCNA staining), migration (Transwell), apoptosis (TUNEL, cleaved caspase-3/Bcl-2), and mechanistic studies (qPCR, FISH). Bioinformatics tools predicted circRNA-miRNA interactions. Data were analyzed using ANOVA and t-tests (SPSS 27.0).

Results: Circ-Myh4_un770 was significantly upregulated in stenotic veins (log2FC > 2, p < 0.001). Knockdown of circ-Myh4_un770 suppressed VSMC proliferation (37% reduction, p < 0.01) and migration (52% reduction, p < 0.05), while promoting apoptosis (2.1-fold increase in cleaved caspase-3, p < 0.01). Conversely, circ-Myh4_un770 overexpression exacerbated VSMC dysfunction. Bioinformatic prediction and expression analyses support an interaction between circ-Myh4_un770 and miR-3593-5p (65% reduction, p < 0.01). miR-3593-5p overexpression phenocopied circ-Myh4_un770 knockdown effects, inhibiting proliferation (41% reduction, p < 0.05) and migration (48% reduction, p < 0.05).

Conclusions: Our study demonstrates that circ-Myh4_un770 contributes to VSMC dysfunction in vein graft stenosis through interaction with miR-3593-5p. These findings suggest that modulating the circ-Myh4_un770/miR-3593-5p axis could represent a strategy to attenuate pathological vascular remodeling. While further validation of direct RNA interactions (e.g., luciferase assays) and human tissue studies are required, our data highlight the potential translational relevance of circ-Myh4_un770 and miR-3593-5p in VGF management.

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Circ-Myh4_un770通过miR-3593-5p调控血管移植狭窄中的VSMC增殖和迁移：血管重构的一种机制

背景：冠状动脉旁路移植术（CABG）是治疗冠心病（CHD）的基础疗法，但由新生内膜增生引起的静脉移植衰竭（VGF）仍然是一个主要的临床挑战。血管平滑肌细胞（VSMC）的增殖和迁移是这种病理的核心，然而环状rna （circRNAs）在VGF中的调节作用尚不清楚。本研究旨在鉴定驱动VSMC功能障碍的环状rna，并探讨其在静脉移植物狭窄中的机制。方法：建立小鼠颈静脉-颈动脉旁路移植术模型。RNA测序鉴定出狭窄静脉与对照组中差异表达的环状RNA。功能验证包括VSMCs中circRNA敲低/过表达、增殖（CCK-8， PCNA染色）、迁移（Transwell）、凋亡（TUNEL, cleaved caspase-3/Bcl-2）和机制研究（qPCR， FISH）。生物信息学工具预测circRNA-miRNA相互作用。数据分析采用方差分析和t检验（SPSS 27.0）。结果：Circ-Myh4_un770在狭窄静脉中显著上调（log2FC > 2, p < 0.001）。敲低circ-Myh4_un770抑制VSMC增殖（减少37%，p < 0.01）和迁移（减少52%，p < 0.05），促进细胞凋亡（cleaved caspase-3增加2.1倍，p < 0.01）。相反，circ-Myh4_un770过表达加重了VSMC功能障碍。生物信息学预测和表达分析支持circ-Myh4_un770和miR-3593-5p之间的相互作用（降低65%，p < 0.01）。miR-3593-5p过表达表型复制circ-Myh4_un770敲低效应，抑制增殖（降低41%，p < 0.05）和迁移（降低48%，p < 0.05）。结论：我们的研究表明circ-Myh4_un770通过与miR-3593-5p的相互作用参与静脉移植狭窄的VSMC功能障碍。这些发现表明，调节circ-Myh4_un770/miR-3593-5p轴可能是一种减轻病理性血管重构的策略。虽然需要进一步验证直接RNA相互作用（例如，荧光素酶测定）和人体组织研究，但我们的数据强调了circ-Myh4_un770和miR-3593-5p在VGF管理中的潜在翻译相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cardiac Surgery 医学-外科

CiteScore

2.90

自引率

12.50%

发文量

976

审稿时长

3-8 weeks

期刊介绍： Journal of Cardiac Surgery (JCS) is a peer-reviewed journal devoted to contemporary surgical treatment of cardiac disease. Renown for its detailed "how to" methods, JCS''s well-illustrated, concise technical articles, critical reviews and commentaries are highly valued by dedicated readers worldwide. With Editor-in-Chief Harold Lazar, MD and an internationally prominent editorial board, JCS continues its 20-year history as an important professional resource. Editorial coverage includes biologic support, mechanical cardiac assist and/or replacement and surgical techniques, and features current material on topics such as OPCAB surgery, stented and stentless valves, endovascular stent placement, atrial fibrillation, transplantation, percutaneous valve repair/replacement, left ventricular restoration surgery, immunobiology, and bridges to transplant and recovery. In addition, special sections (Images in Cardiac Surgery, Cardiac Regeneration) and historical reviews stimulate reader interest. The journal also routinely publishes proceedings of important international symposia in a timely manner.