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Cardiomyocyte Regeneration in Human Myocarditis

Authors :
Andrea Frustaci
Eleonora Foglio
Federica Limana
Michele Magnocavallo
Emanuela Frustaci
Leonardo Lupacchini
Romina Verardo
Source :
Biomedicines, Vol 12, Iss 8, p 1814 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Background: Newly generated cardiomyocytes (NGCs) concur with the recovery of human myocarditis occurring spontaneously in around 50% of cases. However, NGCs decline with age, and their modality of myocardial homing and integration are still unclear. Methods: We retrospectively assessed NGCs 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, and phosphorylated STAT3 (p-STAT3), and Western blot (WB) for HMGB1. Frozen samples were analyzed using 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 and positive immunostaining for cytoplasmic α-sarcomeric actin and connexin-43. Their number/mm2 in relation to age and pathway of integration was 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 comparison to LVEF, was 86.3 ± 10.3/mm2 in patients between 18 and 40 years, 50.4 ± 13.8/mm2 in those between 41 and 60, and 15.1 ± 5.7/mm2 in those between 61 and 80. Control NGCs’ 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 allows for the preservation of the cardiac structure and function.

Details

Language :
English
ISSN :
22279059
Volume :
12
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.2af0d04fe4b4c35a26678e64f39ec97
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines12081814