Chen Yu, Yang Siyuan, Niu Yifan, Cao Tianqing, Yao Yan, Sun Yiming, Chen Mingxing
Department of Cardiology, Northern Jiangsu People's Hospital.
Int Heart J. 2025;66(4):682-689. doi: 10.1536/ihj.24-669.
Increasingly evidence suggests that microRNA (miRNA) plays a pivotal role in coronary artery disease (CAD). This study investigated the abundance of miR-4429 in the serum of CAD patients and explored the function of miR-4429 and its target GNAI2.A total of 164 participants were enrolled. The relative expression levels of miR-4429 were quantified by qRT-PCR. The diagnostic performance and risk factors were analyzed using receiver operating characteristic (ROC) curves and binomial logistic regression (LR). Proliferation and apoptosis were assayed by CCK-8 and flow cytometry in human umbilical vein endothelial cells (HUVEC) induced by oxidized low-density lipoprotein (ox-LDL). The relationship between miR-4429 and GNAI2 was confirmed by dual-luciferase reporter assay and co-transfection.miR-4429 levels were decreased and GNAI2 levels increased in CAD patient serum and ox-LDL-induced HUVEC. miR-4429 was negatively associated with white blood cells (WBC) and C-reactive protein (CRP). ROC curve analysis confirmed the efficacy of miR-4429 and GNAI2 in distinguishing CAD. miR-4429 and GNAI2 were independent predictors for CAD. Restoring miR-4429 reversed the ox-LDL-induced increases in IL-6, MCP-1, and ICAM-1, the suppression of HUVEC proliferation, and the promotion of apoptosis. GNAI2 was a direct target of miR-4429 by dual-luciferase assay. GNAI2 upregulation negated the suppression of cytokines and the protection of cellular function by miR-4429.In summary, this study demonstrates the diagnostic value of miR-4429 and its association with serum inflammation levels in CAD. miR-4429 reversed ox-LDL-induced inflammatory-related cytokines, proliferation, and apoptosis in HUVEC, suggesting miR-4429 may serve as a protective biomarker by targeting the GNAI2 in CAD.
越来越多的证据表明,微小RNA(miRNA)在冠状动脉疾病(CAD)中起关键作用。本研究调查了CAD患者血清中miR-4429的丰度,并探讨了miR-4429及其靶标GNAI2的功能。
共纳入164名参与者。通过qRT-PCR定量miR-4429的相对表达水平。使用受试者工作特征(ROC)曲线和二项逻辑回归(LR)分析诊断性能和危险因素。通过CCK-8和流式细胞术检测氧化低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVEC)中的增殖和凋亡。通过双荧光素酶报告基因测定和共转染证实了miR-4429与GNAI2之间的关系。
CAD患者血清和ox-LDL诱导的HUVEC中miR-4429水平降低,GNAI2水平升高。miR-4429与白细胞(WBC)和C反应蛋白(CRP)呈负相关。ROC曲线分析证实了miR-4429和GNAI2在区分CAD方面的有效性。miR-4429和GNAI2是CAD的独立预测因子。恢复miR-4429可逆转ox-LDL诱导的IL-6、MCP-1和ICAM-1增加、HUVEC增殖抑制和凋亡促进。通过双荧光素酶测定,GNAI2是miR-4429的直接靶标。GNAI2上调消除了miR-4429对细胞因子的抑制和对细胞功能的保护作用。
总之,本研究证明了miR-4429的诊断价值及其与CAD患者血清炎症水平的关联。miR-4429逆转了ox-LDL诱导的HUVEC中炎症相关细胞因子、增殖和凋亡,表明miR-4429可能通过靶向CAD中的GNAI2作为一种保护性生物标志物。