Cardiac troponin I antibodies induce cardiomyocyte damage and alter cell morphology
Circulating heart-reactive autoantibodies (aAbs) detected in a variety of heart diseases (e.g., myocarditis, dilated cardiomyopathy, and myocardial infarction) have been associated with the progression of heart failure and a poor prognosis. However, the underlying mechanisms remain largely unknown....
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| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
14 October 2025
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| In: |
International journal of molecular sciences
Year: 2025, Jahrgang: 26, Heft: 20, Pages: 1-17 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms262010005 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms262010005 Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/26/20/10005 
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| Verfasserangaben: | Jennifer Furkel, Vanessa A. Zirkenbach, Maximilian Knoll, Renate Öttl, Katrin Rein, Amir Abdollahi, Norbert Frey, Mathias H. Konstandin and Ziya Kaya |
| Zusammenfassung: | Circulating heart-reactive autoantibodies (aAbs) detected in a variety of heart diseases (e.g., myocarditis, dilated cardiomyopathy, and myocardial infarction) have been associated with the progression of heart failure and a poor prognosis. However, the underlying mechanisms remain largely unknown. We investigated the effects of murine plasma containing aAbs against cardiac troponin I (cTnI) on neonatal rat cardiomyocytes (NRCMs). An autoimmune response to cTnI in A/J mice was induced, and anti-cTnI-aAbs were quantified. After 21 days, cardiac function, inflammation, fibrosis, and apoptosis were evaluated. In complementary in vitro liquid biopsy experiments, NRCMs were incubated with murine plasma containing high anti-cTnI-aAb levels or corresponding controls. Morphological phenotyping was performed using the C-MORE fluorescent image-based analysis workflow. Immunization with cTnI resulted in high anti-cTnI-aAb production, followed by myocardial inflammation, fibrosis, and impaired ejection fraction. NRCMs exposed to anti-cTnI-aAb-containing plasma showed reduced cell size, altered shape and radius, and elevated rate of dead cells in cell cycle analysis (p < 0.01, for 20% plasma). Together, these findings suggest a direct interaction of anti-cTnI-aAbs on cardiomyocytes, likely promoting adverse myocardial remodeling in vivo. |
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| Beschreibung: | Veröffentlicht: 14. Oktober 2025 Gesehen am 04.12.2025 |
| Beschreibung: | Online Resource |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms262010005 |