- Journal Article
Rights / licenseCreative Commons Attribution-NonCommercial 4.0 International
Aims Newborn mice and humans display transient cardiac regenerative potential that rapidly declines postnatally. Patients who survive a myocardial infarction (MI) often develop chronic heart failure due to the heart's poor regeneration capacity. We hypothesized that the cardiac 'regenerative-to-scarring' transition might be driven by the perinatal shifts observed in the circulating T-cell compartment. Methods and results Post-MI immune responses were characterized in 1- (P1) vs. 7-day-old (P7) mice subjected to left anterior descending artery ligation. Myocardial infarction induced robust early inflammatory responses (36 h post-MI) in both age groups, but neonatal hearts exhibited rapid resolution of inflammation and full functional recovery. The perinatal loss of myocardial regenerative capacity was paralleled by a baseline increase in alpha beta-T cell (CD4(+) and CD8(+)) numbers. Strikingly, P1-infarcted mice reconstituted with adult T-cells shifted to an adult-like healing phenotype, marked by irreversible cardiac functional impairment and increased fibrosis. Infarcted neonatal mice harbouring adult T-cells also had more monocyte-derived macrophage recruitment, as typically seen in adults. At the transcriptome level, infarcted P1 hearts that received isolated adult T-cells showed enriched gene sets linked to fibrosis, inflammation, and interferon-gamma (IFN-gamma) signalling. In contrast, newborn mice that received isolated Ifng(-/-) adult T-cells prior to MI displayed a regenerative phenotype that resembled that of its age-matched untreated controls. Conclusion Physiological T-cell development or adoptive transfer of adult IFN-gamma-producing T-cells into neonates contributed to impaired cardiac regeneration and promoted irreversible structural and functional cardiac damage. These findings reveal a trade-off between myocardial regenerative potential and the development of T-cell competence. Show more
Journal / seriesEuropean Heart Journal
Pages / Article No.
PublisherOxford University Press
SubjectCardiac regeneration; Immune system; Myocardial infarction; T-cells; Wound healing
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