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黏膜相关恒定T细胞与冠状动脉疾病中的心肌缺血和重塑相关。

Mucosal-associated invariant T cells correlate with myocardial ischaemia and remodelling in coronary artery disease.

作者信息

Wang Jiafu, Li Song, Zhou Xianling, Wu Hongxing, Ouyang Xiaolan, Huang Zhuoshan, Peng Long, Chen Qian, Wu Yuman, Li Zhitong, Peng Ziyi, Yang Yi, Lu Yan, Tang Xixiang, Li Yue, Li Suhua

机构信息

Department of Cardiovascular Medicine The Third Affiliated Hospital of Sun Yat-sen University Guangzhou China.

Department of Clinical Immunology The Third Affiliated Hospital of Sun Yat-sen University Guangzhou China.

出版信息

Clin Transl Immunology. 2025 Mar 24;14(3):e70029. doi: 10.1002/cti2.70029. eCollection 2025.

Abstract

OBJECTIVES

Myocardial ischaemia and remodelling are major contributors to the progression and mortality of coronary artery disease (CAD). Previous studies have shown immune cell alterations in CAD patients, but their characteristics and associations with myocardial ischaemia and remodelling remain unclear.

METHODS

We compared immune cell changes among patients without CAD, those with CAD and those with CAD and heart failure (HF).

RESULTS

We found a progressive reduction in circulating mucosal-associated invariant T (MAIT) cells across the three patient groups. MAIT cells exhibited increased expression of activation markers (CD69 and PD-1) and cytotoxic molecules (such as granzyme B). The features of MAIT cells were correlated positively with worsening clinical indicators of myocardial ischaemia and remodelling, including the Gensini score, cTnI, NT-proBNP, LVEF and E/e'. Additionally, the reduction, activation and cytotoxicity of MAIT cells were associated with indicators of myocardial fibrosis (sST2, Gal-3, PICP and PIIINP), a central pathological mechanism of myocardial remodelling. Finally, we preliminarily explored potential triggers for MAIT cell abnormalities in CAD patients and found that impaired intestinal barrier function and increased circulating bacterial antigens may contribute to these changes.

CONCLUSIONS

During CAD progression, we observed a decrease in circulating MAIT cells. Enhanced activation and cytotoxicity of MAIT cells are associated with myocardial ischaemia and remodelling in CAD patients with heart failure, potentially triggered by gut microbial leakage. Our findings suggest a novel strategy for monitoring and intervention in disease progression.

摘要

目的

心肌缺血和重塑是冠状动脉疾病(CAD)进展和死亡的主要促成因素。既往研究显示CAD患者存在免疫细胞改变,但其特征以及与心肌缺血和重塑的关联仍不明确。

方法

我们比较了无CAD患者、CAD患者以及CAD合并心力衰竭(HF)患者的免疫细胞变化。

结果

我们发现三组患者循环中的黏膜相关恒定T(MAIT)细胞逐渐减少。MAIT细胞表现出激活标志物(CD69和PD-1)及细胞毒性分子(如颗粒酶B)表达增加。MAIT细胞的这些特征与心肌缺血和重塑的临床指标恶化呈正相关,这些指标包括Gensini评分、肌钙蛋白I(cTnI)、N末端B型利钠肽原(NT-proBNP)、左心室射血分数(LVEF)和E/A'比值。此外,MAIT细胞的减少、激活和细胞毒性与心肌纤维化指标(可溶性ST2、半乳糖凝集素-3、I型前胶原羧基端前肽和III型前胶原N端肽)相关,心肌纤维化是心肌重塑的核心病理机制。最后,我们初步探究了CAD患者MAIT细胞异常的潜在触发因素,发现肠道屏障功能受损和循环中细菌抗原增加可能导致这些变化。

结论

在CAD进展过程中,我们观察到循环MAIT细胞减少。MAIT细胞激活和细胞毒性增强与CAD合并心力衰竭患者的心肌缺血和重塑相关,可能由肠道微生物渗漏触发。我们的研究结果提示了一种监测和干预疾病进展的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/11931450/d0675daad6b4/CTI2-14-e70029-g004.jpg

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