Canonical Wnt/β-catenin signaling in epicardial fibrosis of failed pediatric heart allografts with diastolic dysfunction

Bo Ye, Yao Ge, Gregory Perens, Longsheng Hong, Haodong Xu, Michael C. Fishbein, Faqian Li

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background: Failed pediatric heart allografts with diastolic dysfunction exhibit severe epicardial fibrosis. The molecular mechanism underlying this process is poorly understood. Canonical Wnt/β-catenin signaling plays an important role in epithelial-mesenchymal transition and is implicated in fibrosing diseases. In this study, we tested the hypothesis that canonical Wnt/β-catenin signaling is activated in epicardial fibrosis of end-stage dysfunctional pediatric allografts. Methods: Fourteen explanted heart grafts of 12 patients who had undergone 14 heart transplantations were used for immunohistochemical staining of β-catenin and its nuclear binding partners, T-cell factor/lymphoid enhancer factor family transcriptional factors. Fourteen age-matched native hearts from patients who had undergone first heart transplantation without evidence of epicardial fibrosis were used as controls. Results and conclusions: Epicardial fibroblasts from explanted allografts demonstrated nuclear accumulation of β-catenin. These cells also showed nuclear positivity for T-cell factor 4. No T-cell factor 3 expression was present in the epicardium. T-cell factor 1 and lymphoid enhancer factor 1 were observed in lymphocytes, but not in other cell types of the epicardium. These findings suggest an association between canonical Wnt/beta-catenin signaling and epicardial fibrosis of failed pediatric heart allografts. Should activation of this pathway be shown to be causal to epicardial fibrosis in this setting, then inhibition of this pathway may help to prevent this devastating process.

Original languageEnglish (US)
Pages (from-to)54-57
Number of pages4
JournalCardiovascular Pathology
Volume22
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Allograft
  • Epicardium
  • Fibrosis
  • Heart failure
  • Heart transplant
  • LEF/TCF
  • Pediatric
  • Wnt signaling
  • β-Catenin

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