Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis

Vasco Sampaio-Pinto, Sílvia C. Rodrigues, Tiago L. Laundos, Elsa D. Silva, Francisco Vasques-Nóvoa, Ana C. Silva, Rui J. Cerqueira, Tatiana P. Resende, Nicola Pianca, Adelino Leite-Moreira, Gabriele D'Uva, Sólveig Thorsteinsdóttir, Perpétua Pinto-do-Ó, Diana S. Nascimento

Research output: Contribution to journalArticlepeer-review

Abstract

So far, opposing outcomes have been reported following neonatal apex resection in mice, questioning the validity of this injury model to investigate regenerative mechanisms. We performed a systematic evaluation, up to 180 days after surgery, of the pathophysiological events activated upon apex resection. In response to cardiac injury, we observed increased cardiomyocyte proliferation in remote and apex regions, neovascularization, and local fibrosis. In adulthood, resected hearts remain consistently shorter and display permanent fibrotic tissue deposition in the center of the resection plane, indicating limited apex regrowth. However, thickening of the left ventricle wall, explained by an upsurge in cardiomyocyte proliferation during the initial response to injury, compensated cardiomyocyte loss and supported normal systolic function. Thus, apex resection triggers both regenerative and reparative mechanisms, endorsing this injury model for studies aimed at promoting cardiomyocyte proliferation and/or downplaying fibrosis. In this article, Nascimento and colleagues demonstrate that neonatal apex resection stimulates cardiomyocyte proliferation and permanent scarring in the apex. Newly formed cardiomyocytes compensate muscle loss by resection, and resected hearts recover functional competence in adulthood. These findings endorse this model for studies aiming to block cardiac fibrosis and/or favoring CM proliferation.

Original languageEnglish
Pages (from-to)860-874
Number of pages15
JournalStem Cell Reports
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 13 2018

Keywords

  • cardiac fibroblasts
  • cardiac injury response
  • cardiac regeneration
  • cardiomyocyte proliferation
  • extracellular matrix
  • fibrosis
  • neonatal apex resection
  • neovascularization
  • stereology

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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