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

## TL;DR

Autoantibodies against cardiac troponin I can damage heart cells and change their shape, contributing to heart disease.

## Contribution

This study demonstrates that anti-cTnI autoantibodies directly affect cardiomyocyte morphology and viability.

## Key findings

- Anti-cTnI autoantibodies induce myocardial inflammation, fibrosis, and reduced ejection fraction in mice.
- Exposure to anti-cTnI autoantibodies reduces cardiomyocyte size and increases cell death in vitro.
- Morphological changes in cardiomyocytes suggest a direct interaction with anti-cTnI autoantibodies.

## 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.