Journal Article DKFZ-2025-02229

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Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology.

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2025
Molecular Diversity Preservation International Basel

International journal of molecular sciences 26(20), 10005 () [10.3390/ijms262010005]
 GO

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.

Keyword(s): Animals (MeSH) ; Myocytes, Cardiac: pathology (MeSH) ; Myocytes, Cardiac: immunology (MeSH) ; Myocytes, Cardiac: metabolism (MeSH) ; Troponin I: immunology (MeSH) ; Autoantibodies: immunology (MeSH) ; Autoantibodies: blood (MeSH) ; Rats (MeSH) ; Mice (MeSH) ; Fibrosis (MeSH) ; Apoptosis (MeSH) ; Animals, Newborn (MeSH) ; Male (MeSH) ; autoantibodies ; cardiomyocytes ; heart failure ; morphology ; troponin I ; Troponin I ; Autoantibodies

Classification:

Note: #EA:E210#

Contributing Institute(s):
  1. E210 KKE Translationale Radioonkologie (E210)
  2. DKTK HD zentral (HD01)
Research Program(s):
  1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2025
Database coverage:
Medline ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2025-10-29, last modified 2025-10-30



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