Version 1
: Received: 8 July 2024 / Approved: 8 July 2024 / Online: 9 July 2024 (14:04:14 CEST)
How to cite:
Frustaci, A.; Foglio, E.; Limana, F.; Magnocavallo, M.; Frustaci, E.; Lupacchini, L.; Verardo, R. Cardiomyocyte Regeneration in Human Myocarditis. Preprints2024, 2024070642. https://doi.org/10.20944/preprints202407.0642.v1
Frustaci, A.; Foglio, E.; Limana, F.; Magnocavallo, M.; Frustaci, E.; Lupacchini, L.; Verardo, R. Cardiomyocyte Regeneration in Human Myocarditis. Preprints 2024, 2024070642. https://doi.org/10.20944/preprints202407.0642.v1
Frustaci, A.; Foglio, E.; Limana, F.; Magnocavallo, M.; Frustaci, E.; Lupacchini, L.; Verardo, R. Cardiomyocyte Regeneration in Human Myocarditis. Preprints2024, 2024070642. https://doi.org/10.20944/preprints202407.0642.v1
APA Style
Frustaci, A., Foglio, E., Limana, F., Magnocavallo, M., Frustaci, E., Lupacchini, L., & Verardo, R. (2024). Cardiomyocyte Regeneration in Human Myocarditis. Preprints. https://doi.org/10.20944/preprints202407.0642.v1
Chicago/Turabian Style
Frustaci, A., Leonardo Lupacchini and Romina Verardo. 2024 "Cardiomyocyte Regeneration in Human Myocarditis" Preprints. https://doi.org/10.20944/preprints202407.0642.v1
Abstract
Background : Newly generated cardiomyocytes (NGC) concur to recovery of human myocarditis. However,
Methods: We retrospectively assessed NGC in 213 consecutive patients with endomyocardial biopsy denoting acute myocarditis, with normal coronaries and valves. Tissue samples were processed for histology (H&E), immunohistochemistry for the evaluation of inflammatory infiltrates, immunostaining for alpha-sarcomeric-actin, junctional connexin-43, Ki-67, phosphorylated STAT3 (p-STAT3) and Western Blot (WB) for HMGB1. Frozen samples were analyzed with polymerase chain reaction (PCR) for cardiotropic viruses. Controls included 20 normal surgical biopsies.
Results: NGCs were defined as small myocytes (diameter < 10 µm) with nuclear positivity to Ki-67 and p-STAT3, positive immunostaining for cytoplasmic α-sarcomeric actin and connexin 43. Their number/mm2 in relation with age and pathway of integration were evaluated. NGCs crossed the membrane and grew integrated within the empty necrotic myocytes. NGC mean diameter was 6.6 ± 3.34 vs 22.5 ± 3.11 µm adult cells; their number, in comparable LVEF, was 86.3 ± 10.3/mm2 in patients between 10 and 40 years; 50.4 ±13.8/mm2 in those between 41 and 60; 15.1 ± 5.7/ mm2 in those between 61 and 80; control NGC mean diameter was 0.2± 0.2/mm2. PCR was positive for viral genomes in 16% of cases; NGCs were not statistically different in viral and non-viral myocarditis. WB analysis revealed a higher expression of HMGB1 in myocarditis compared to myocardial controls.
Conclusions: NGCs are constantly recognizable in acute human myocarditis. Their number declines with age. Their integration within necrotic myocytes consents preservation of cardiac structure and function.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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