Cardiomyocyte regeneration in human myocarditis

Abstract Background Newly generated cardiomyocytes (NGC) concur to recovery of human myocarditis. Purpose describe NGC’s contribute with age and their modality of myocardial homing and integration. Methods We retrospectively assessed NGC in 213 consecutive patients with endomyocardial biopsy diagnostic for myocarditis, normal coronaries and valves. Tissue samples were processed for histology and immune-histochemistry for CD3+ T lymphocytes, 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. NGC were defined as small myocytes (diameter < 10 µ) with nuclear positivity to Ki-67 and p-STAT3, positive immunostaining for cytoplasmic alpha-sarcomeric-actin and connexin 43. Their number/mm2, relation with age and pathway of integration were evaluated. Results PCR was positive for viral genomes in 16% of cases. 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 were 0.2± 0.2/mm2 ; NGC were no statistically different in viral and non-viral myocarditis. HMGB1 and STAT-3 were remarkably higher than controls. NGC crossed the membrane and grew integrated within the empty necrotic myocytes. 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.