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微小RNA-27b-3p与闭塞性动脉硬化相关,并通过靶向衔接蛋白Gab1促进动脉平滑肌细胞的增殖和迁移。

MiR-27b-3p Correlates with Arteriosclerosis Obliterans and Promotes the Proliferation and Migration of Arterial Smooth Muscle Cells by Targeting GAB1.

作者信息

Xu Tuo, Zheng Changwei, Wu Yongkang, Chen Zhengde, Chen Xiaodong

机构信息

Department of Vascular and Thyroid Surgery, The Affiliated Hospital of Guangdong Medical University.

出版信息

Int Heart J. 2025;66(4):690-698. doi: 10.1536/ihj.24-806.

DOI:10.1536/ihj.24-806
PMID:40738709
Abstract

Patients with atherosclerosis obliterans (ASO) are at risk of amputation or even death if timely treatment is not provided; current clinical treatments for ASO have certain disadvantages. This study aimed to ascertain the function of miR-27b-3p in ASO to provide novel insights for ASO treatment.The expression of miR-27b-3p in the serum of 117 ASO subjects and 80 healthy individuals was assessed by polymerase chain reaction. Risk factors for coronary artery disease (CAD) in ASO were assessed by multivariate logistic regression analysis. The atherosclerosis cell model was conducted using human vascular smooth muscle cells (HVSMCs) induced with oxidized low-density lipoprotein (ox-LDL). The interaction relationship between miR-27b-3p and GAB1 was assessed using a dual-luciferase reporter assay. HVSMC proliferation and migration were analyzed using the cell counting kit-8 and transwell assay.MiR-27b-3p was upregulated in ASO; it was correlated with ASO severity indicators (ankle-brachial index level and Fontaine stage) and identified as a risk factor for CAD incidence in ASO. Ox-LDL induction in HVSMCs promoted HVSMC proliferation and migration. Overexpression of miR-27b-3p facilitated the proliferation and migration of ox-LDL-induced HVSMCs, which were attenuated by GAB1 overexpression.The upregulation of miR-27b-3p in ASO was correlated with ASO severity and served as a risk factor for CAD in patients with ASO. The potential regulatory mechanism of miR-27b-3p in ASO was the acceleration of vascular smooth muscle cell proliferation and migration by targeting GAB1.

摘要

如果不及时治疗,闭塞性动脉粥样硬化(ASO)患者有截肢甚至死亡的风险;目前ASO的临床治疗存在一定弊端。本研究旨在确定miR-27b-3p在ASO中的作用,为ASO治疗提供新的见解。通过聚合酶链反应评估117例ASO患者和80例健康个体血清中miR-27b-3p的表达。采用多因素逻辑回归分析评估ASO患者冠状动脉疾病(CAD)的危险因素。利用氧化型低密度脂蛋白(ox-LDL)诱导的人血管平滑肌细胞(HVSMC)建立动脉粥样硬化细胞模型。采用双荧光素酶报告基因检测法评估miR-27b-3p与GAB1之间的相互作用关系。使用细胞计数试剂盒-8和Transwell实验分析HVSMC的增殖和迁移。miR-27b-3p在ASO中表达上调;它与ASO严重程度指标(踝臂指数水平和Fontaine分期)相关,并被确定为ASO患者CAD发病的危险因素。ox-LDL诱导HVSMC促进其增殖和迁移。miR-27b-3p的过表达促进了ox-LDL诱导的HVSMC的增殖和迁移,而GAB1的过表达则减弱了这种作用。ASO中miR-27b-3p的上调与ASO严重程度相关,并作为ASO患者CAD的危险因素。miR-27b-3p在ASO中的潜在调控机制是通过靶向GAB1加速血管平滑肌细胞的增殖和迁移。

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