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长链非编码 RNA NEAT1/miR-211/IL-10 轴调节急性心肌梗死患者外周血单个核细胞炎症反应。

LncRNA NEAT1/miR-211/IL-10 Axis Regulates Inflammation of Peripheral Blood Mononuclear Cells in Acute Myocardial Infarction.

机构信息

Department of Cardiovascular Medicine, Affiliated Hospital of Jiangnan University.

Department of Cardiovascular Medicine, No. 904 Hospital of the Joint Logistics Support Force of PLA.

出版信息

Int Heart J. 2024;65(3):498-505. doi: 10.1536/ihj.23-368.

Abstract

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1β and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.

摘要

本研究旨在通过 miR-211/白细胞介素 10(IL-10)轴探讨长链非编码 RNA(lncRNA)核斑蛋白组装转录物 1(NEAT1)在急性心肌梗死(AMI)患者中的表达及其炎症调节机制。共纳入 75 名参与者:对照组 25 名健康人,SAP 组 25 名稳定型心绞痛(SAP)患者,AMI 组 25 名 AMI 患者。实时 qPCR 检测 NEAT1、miR-211 和 IL-10 的 mRNA 表达水平。双荧光素酶报告基因实验证实 miR-211、NEAT1 和 IL-10 之间的相互作用,Western blot 检测蛋白表达。AMI 患者外周血单个核细胞(PBMCs)中高表达 NEAT1 与血清肌酸激酶同工酶-MB(CK-MB)、心肌肌钙蛋白 I(cTnI)、肿瘤坏死因子-α(TNF-α)、IL-6 和 IL-1β呈负相关,与左心室射血分数(LVEF)呈正相关。在 THP-1 细胞中,证实 miR-211 靶向并抑制 IL-10 表达。NEAT1 敲低和 miR-211 模拟显著降低 IL-10 蛋白水平,而抗 miR-211 显著增加 IL-10 蛋白水平。重要的是,miR-211 水平与 NEAT1 和 IL-10 水平呈负相关,而 AMI 患者 PBMCs 中 NEAT1 表达水平与 IL-10 水平呈正相关。在 AMI 患者的 PBMCs 中,lncRNA NEAT1 高表达,NEAT1 通过 miR-211/IL-10 轴抑制 AMI 患者 PBMCs 的炎症反应。

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