Zhu Tianyu, Ding Ying, Wu Xiaohui, Li Yan, Cheng Guanliang, Wang Ning, Yang Quan, Zhang Wenchao, Chen Xuezhi, Liu Xiaohui
Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China.
Department of Nephrology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Centre for Geriatric Diseases, Beijing, 100853, P.R. China.
BMC Cardiovasc Disord. 2025 May 7;25(1):354. doi: 10.1186/s12872-025-04790-w.
This study aims to investigate the expression of Pentraxin 3 (PTX3) and Nod-like receptor family pyrin domain-containing 3 (NLRP3) in myocarditis and to elucidate their roles and potential interplay in the pathogenesis of myocarditis.
Immunofluorescence staining was performed on myocardial autopsy specimens from deceased patients with severe myocarditis or severe trauma. H9C2 cardiomyocytes were divided into five groups: Control, Lipopolysaccharide (LPS), LPS + PTX3 overexpression, LPS + small interfering RNA targeting PTX3 (si-PTX3), and LPS + PTX3 overexpression + si-NLRP3. The expression levels of PTX3 and NLRP3 at the RNA level were quantified using quantitative real-time polymerase chain reaction (qPCR), while protein expression was assessed via western blot. The concentrations of interleukin-1β (IL-1β) and IL-18 were determined by enzyme-linked immunosorbent assay (ELISA). Macrophages migration was evaluated using Transwell assays.
Immunofluorescence staining revealed co-localization and increased expression of PTX3 and NLRP3 in the myocardium of patients with severe myocarditis. In vitro experiments demonstrated that PTX3 enhanced the expression of NLRP3, IL-1β, and IL-18 in LPS-stimulated cardiomyocytes. Furthermore, PTX3 was shown to promote macrophage migration by regulating NLRP3 expression, as assessed by Transwell assays.
Our findings suggest that PTX3-mediated NLRP3 activation contributes to inflammatory responses and promotes macrophage migration in myocarditis. This study provides a foundation for future investigations into PTX3-targeted therapies for myocarditis.
本研究旨在调查五聚体3（PTX3）和含NOD样受体家族吡啉结构域3（NLRP3）在心肌炎中的表达，并阐明它们在心肌炎发病机制中的作用及潜在相互作用。
对死于严重心肌炎或严重创伤的患者的心肌尸检标本进行免疫荧光染色。将H9C2心肌细胞分为五组：对照组、脂多糖（LPS）组、LPS + PTX3过表达组、LPS +靶向PTX3的小干扰RNA（si-PTX3）组以及LPS + PTX3过表达+ si-NLRP3组。使用定量实时聚合酶链反应（qPCR）定量PTX3和NLRP3在RNA水平的表达，同时通过蛋白质印迹法评估蛋白质表达。采用酶联免疫吸附测定（ELISA）测定白细胞介素-1β（IL-1β）和IL-18的浓度。使用Transwell实验评估巨噬细胞迁移。
免疫荧光染色显示，严重心肌炎患者心肌中PTX3和NLRP3共定位且表达增加。体外实验表明，PTX3增强了LPS刺激的心肌细胞中NLRP3、IL-1β和IL-18的表达。此外，通过Transwell实验评估，PTX3被证明可通过调节NLRP3表达促进巨噬细胞迁移。
我们的研究结果表明，PTX3介导的NLRP3激活有助于炎症反应，并促进心肌炎中的巨噬细胞迁移。本研究为未来针对心肌炎的PTX3靶向治疗研究奠定了基础。
