TY - JOUR
AU - Furkel, Jennifer
AU - Zirkenbach, Vanessa A
AU - Knoll, Maximilian
AU - Öttl, Renate
AU - Rein, Katrin
AU - Abdollahi, Amir
AU - Frey, Norbert
AU - Konstandin, Mathias H
AU - Kaya, Ziya
TI - Cardiac Troponin I Antibodies Induce Cardiomyocyte Damage and Alter Cell Morphology.
JO - International journal of molecular sciences
VL - 26
IS - 20
SN - 1422-0067
CY - Basel
PB - Molecular Diversity Preservation International
M1 - DKFZ-2025-02229
SP - 10005
PY - 2025
N1 - #EA:E210#
AB - 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
KW - Animals
KW - Myocytes, Cardiac: pathology
KW - Myocytes, Cardiac: immunology
KW - Myocytes, Cardiac: metabolism
KW - Troponin I: immunology
KW - Autoantibodies: immunology
KW - Autoantibodies: blood
KW - Rats
KW - Mice
KW - Fibrosis
KW - Apoptosis
KW - Animals, Newborn
KW - Male
KW - autoantibodies (Other)
KW - cardiomyocytes (Other)
KW - heart failure (Other)
KW - morphology (Other)
KW - troponin I (Other)
KW - Troponin I (NLM Chemicals)
KW - Autoantibodies (NLM Chemicals)
LB - PUB:(DE-HGF)16
C6 - pmid:41155300
DO - DOI:10.3390/ijms262010005
UR - https://inrepo02.dkfz.de/record/305559
ER -