PUBLICATION

Rapamycin attenuates pathological hypertrophy caused by an absence of trabecular formation

Authors
Fleming, N.D., Samsa, L.A., Hassel, D., Qian, L., Liu, J.
ID
ZDB-PUB-180607-3
Date
2018
Source
Scientific Reports   8: 8584 (Journal)
Registered Authors
Fleming, Nicole, Hassel, David, Liu, Jiandong, Samsa, Leigh Ann
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Hypertrophy/embryology
  • Hypertrophy/genetics
  • Hypertrophy/prevention & control*
  • Immunosuppressive Agents/pharmacology
  • Morphogenesis/drug effects
  • Morphogenesis/genetics
  • Mutation
  • Myocardium/metabolism*
  • Myocardium/pathology
  • Receptor, ErbB-2/genetics
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Sirolimus/pharmacology*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
PubMed
29872120 Full text @ Sci. Rep.
Abstract
Cardiac trabeculae are mesh-like muscular structures within ventricular walls. Subtle perturbations in trabeculation are associated with many congenital heart diseases (CHDs), and complete failure to form trabeculae leads to embryonic lethality. Despite the severe consequence of an absence of trabecular formation, the exact function of trabeculae remains unclear. Since ErbB2 signaling plays a direct and essential role in trabecular initiation, in this study, we utilized the erbb2 zebrafish mutant as a model to address the function of trabeculae in the heart. Intriguingly, we found that the trabeculae-deficient erbb2 mutant develops a hypertrophic-like (HL) phenotype that can be suppressed by inhibition of Target of Rapamycin (TOR) signaling in a similar fashion to adult mammalian hearts subjected to mechanical overload. Further, cell transplantation experiments demonstrated that erbb2 mutant cells in an otherwise wildtype heart did not undergo hypertrophy, indicating that erbb2 mutant HL phenotypes are due to a loss of trabeculae. Together, we propose that trabeculae serve to enhance contractility and that defects in this process lead to wall-stress induced hypertrophic remodeling.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping