{
    "abstract": "Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through \nTotal immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments.\nAfter the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching.\nAnti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.",
    "authors": [
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.\nDepartment of Rheumatology and Immunology The First Hospital of Lanzhou University Lanzhou Gansu China.\nThe First Clinical Medical College Lanzhou University Lanzhou Gansu China.",
            "firstname": "Hao",
            "initials": "H",
            "lastname": "Zhang"
        },
        {
            "affiliation": "Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.\nDepartment of Cardiovascular Medicine, Heart Failure Center, Ruijin Hospital, and Ruijin Hospital Lu Wan Branch Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Yunjing",
            "initials": "Y",
            "lastname": "Shi"
        },
        {
            "affiliation": "Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.\nDepartment of Cardiovascular Medicine, Heart Failure Center, Ruijin Hospital, and Ruijin Hospital Lu Wan Branch Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Yingze",
            "initials": "Y",
            "lastname": "Fan"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Dehao",
            "initials": "D",
            "lastname": "Zhu"
        },
        {
            "affiliation": "Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.\nDepartment of Cardiovascular Medicine, Heart Failure Center, Ruijin Hospital, and Ruijin Hospital Lu Wan Branch Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Zeping",
            "initials": "Z",
            "lastname": "Qiu"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Huihui",
            "initials": "H",
            "lastname": "Chi"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Qiongyi",
            "initials": "Q",
            "lastname": "Hu"
        },
        {
            "affiliation": "Department of Laboratory Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Liangzhe",
            "initials": "L",
            "lastname": "Xie"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Yue",
            "initials": "Y",
            "lastname": "Sun"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Honglei",
            "initials": "H",
            "lastname": "Liu"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Xiaobing",
            "initials": "X",
            "lastname": "Cheng"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Junna",
            "initials": "J",
            "lastname": "Ye"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Hui",
            "initials": "H",
            "lastname": "Shi"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Zhuochao",
            "initials": "Z",
            "lastname": "Zhou"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Jianfen",
            "initials": "J",
            "lastname": "Meng"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Jialin",
            "initials": "J",
            "lastname": "Teng"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Chengde",
            "initials": "C",
            "lastname": "Yang"
        },
        {
            "affiliation": "Department of Cardiovascular Medicine, Heart Failure Center, Ruijin Hospital, and Ruijin Hospital Lu Wan Branch Shanghai Jiao Tong University School of Medicine Shanghai China.",
            "firstname": "Wei",
            "initials": "W",
            "lastname": "Jin"
        },
        {
            "affiliation": "Department of Rheumatology and Immunology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.\nShanghai Hospital of Civil Aviation Administration of China Shanghai China.",
            "firstname": "Yutong",
            "initials": "Y",
            "lastname": "Su"
        }
    ],
    "conclusions": "Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.",
    "copyrights": "\u00a9 2024 The Author(s). Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.",
    "doi": "10.1002/cti2.1525",
    "journal": "Clinical & translational immunology",
    "keywords": [
        "anti\u2010signal recognition particle antibody",
        "left ventricular diastolic dysfunction",
        "mitochondrial injury",
        "myositis",
        "reactive oxygen species"
    ],
    "methods": null,
    "publication_date": "2024-08-14",
    "pubmed_id": "39139496\n2432596\n25963141\n27147697\n20826015\n32941250\n30992170\n14747766\n34273157\n37542301\n29848629\n21400483\n20506493\n34508561\n24041831\n30309969\n30074107\n24491486\n33093664\n31292376\n24429180\n26502301\n23908445\n16469117\n10956670\n15829407\n9202053\n17114501\n29409987\n30856000\n36613900\n33176457\n33882692\n28623559\n32110496\n1090839\n15099594",
    "results": "After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching.",
    "title": "Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury.",
    "xml": "<Element 'PubmedArticle' at 0x788503025260>"
}