Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology

Furkel, Jennifer; Zirkenbach, Vanessa A.; Knoll, Maximilian; Öttl, Renate; Rein, Katrin; Abdollahi, Amir; Frey, Norbert; Konstandin, Mathias H.; Kaya, Ziya

doi:10.3390/ijms262010005

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Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology

by

Jennifer Furkel

^{1,2,3,4,5,6,†},

Vanessa A. Zirkenbach

^1,2,†

,

Maximilian Knoll

^3,4,5,6

,

Renate Öttl

¹,

Katrin Rein

^3,4,5,6,

Amir Abdollahi

^3,4,5,6,

Norbert Frey

^1,2,

Mathias H. Konstandin

^1,2,*,‡ and

Ziya Kaya

^1,2,*,‡

¹

Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, 69120 Heidelberg, Germany

²

German Center for Cardiovascular Research (DZHK), Site Heidelberg/Mannheim, 69120 Heidelberg, Germany

³

German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

⁴

CCU Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

⁵

Division of Molecular and Translational Radiation Oncology, Department of Radiation Oncology, Heidelberg Faculty of Medicine (MFHD) and Heidelberg University Hospital (UKHD), Heidelberg Ion-Beam Therapy Center (HIT), 69120 Heidelberg, Germany

⁶

Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Oncology (NCRO), German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD), 69120 Heidelberg, Germany

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(20), 10005; https://doi.org/10.3390/ijms262010005 (registering DOI)

Submission received: 27 August 2025 / Revised: 8 October 2025 / Accepted: 9 October 2025 / Published: 14 October 2025

(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pathology, Diagnostics, and Therapeutics)

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Abstract

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.

Keywords: autoantibodies; cardiomyocytes; heart failure; morphology; troponin I

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MDPI and ACS Style

Furkel, J.; Zirkenbach, V.A.; Knoll, M.; Öttl, R.; Rein, K.; Abdollahi, A.; Frey, N.; Konstandin, M.H.; Kaya, Z. Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology. Int. J. Mol. Sci. 2025, 26, 10005. https://doi.org/10.3390/ijms262010005

AMA Style

Furkel J, Zirkenbach VA, Knoll M, Öttl R, Rein K, Abdollahi A, Frey N, Konstandin MH, Kaya Z. Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology. International Journal of Molecular Sciences. 2025; 26(20):10005. https://doi.org/10.3390/ijms262010005

Chicago/Turabian Style

Furkel, Jennifer, Vanessa A. Zirkenbach, Maximilian Knoll, Renate Öttl, Katrin Rein, Amir Abdollahi, Norbert Frey, Mathias H. Konstandin, and Ziya Kaya. 2025. "Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology" International Journal of Molecular Sciences 26, no. 20: 10005. https://doi.org/10.3390/ijms262010005

APA Style

Furkel, J., Zirkenbach, V. A., Knoll, M., Öttl, R., Rein, K., Abdollahi, A., Frey, N., Konstandin, M. H., & Kaya, Z. (2025). Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology. International Journal of Molecular Sciences, 26(20), 10005. https://doi.org/10.3390/ijms262010005

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Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology

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