Rapamycin attenuates pathological hypertrophy caused by an absence of trabecular formation

We found that the trabeculae-deficient erbb2 mutant develops a hypertrophic-like phenotype that can be suppressed by inhibition of Target of Rapamycin signaling in a similar fashion to adult mammalian hearts subjected to mechanical overload

Nicole D. Fleming; Leigh A. Samsa; David Hassel; Li Qian; Jiandong Liu


Scholarcy highlights

  • The function of the heart is intimately linked to its structure
  • We found that erbb mutant ventricles exhibit an increase in ventricular cardiomyocyte cross-sectional area and myofibril size
  • We present in vivo evidence that cardiac trabeculae have an important physiological function during embryonic heart development
  • We found erbb mutant ventricles exhibit an increase in ventricular CM cross-sectional area and myofibril size, likely due to an absence of trabecular formation, suggesting that trabeculae-deficient ventricles undergo hypertrophy to stabilize the workload/cardiac output imbalance in the heart
  • It has been speculated that cardiac trabeculae serve to increase cardiac output and facilitate the exchange of oxygen and nutrients prior to formation of the coronary vasculature
  • There was no significant difference in Z-line length or the distance between Z-lines between transplanted control and erbb mutant cardiomyocytes
  • The early embryonic lethality of these systems disallows for detailed characterization of the trabeculae-deficient hearts at a cellular level
  • Because of the transparency of the zebrafish embryos and the ease of genetic manipulation, the unique HL phenotype caused by the absence of trabeculae in ErbB2-deficient larvae will provide us a great opportunity to use zebrafish as a model to assess molecular events and mechano-transduction signaling pathways involved in congenital heart diseases-associated hypertrophic cardiomyopathy

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