ZFIN ID: ZDB-PUB-190528-20
Ventricular remodeling of single-chambered myh6-/- adult zebrafish hearts occurs via a hyperplastic response and is accompanied by elastin deposition in the atrium
Sarantis, P., Gaitanaki, C., Beis, D.
Date: 2019
Source: Cell and tissue research   378(2): 279-288 (Journal)
Registered Authors: Beis, Dimitris
Keywords: Elastin, Heart, Hyperplasia, Hypertrophy, Zebrafish, myh6
MeSH Terms:
  • Animals
  • Disease Models, Animal*
  • Elastin/metabolism*
  • Heart Atria*/metabolism
  • Heart Atria*/pathology
  • Hyperplasia/metabolism*
  • Hypertrophy, Left Ventricular/pathology*
  • Hypertrophy, Right Ventricular/pathology*
  • Mutation
  • Myocytes, Cardiac/pathology
  • Myosin Heavy Chains/genetics*
  • Zebrafish
  • Zebrafish Proteins/genetics*
PubMed: 31129720 Full text @ Cell Tissue Res.
Zebrafish (Danio rerio) is widely used as an animal model to understand the pathophysiology of cardiovascular diseases. Here, we present the adult cardiac phenotype of weak atrium, myh6-/-, which carry mutations in the zebrafish atrial myosin heavy chain. Homozygous mutants survive to adulthood and are fertile despite their initial weak atrial beat. In adult mutants, the atrium remains hypoplastic and shows elastin deposition while mutant ventricles exhibit increased size. In mammals, hypertrophy is the most common mechanism resulting in cardiomegaly. Using immunohistochemistry and confocal microscopy to measure cardiomyocyte cell size, density and proliferation, we show that the enlargement of the myh6-/- ventricle is predominantly due to hyperplasia. However, we identified similar transcriptional profiles to the mammalian hypertrophy response via RT-PCR of the hyperplastic ventricles. Furthermore, we show activation of the ER-stress pathway by western blot analysis. In conclusion, we can assume, based on our model, that molecular signaling pathways associated with hypertrophy in mammals, in combination with ER-stress activation, result in hyperplasia in zebrafish. In addition, to our knowledge, this is the first time to report elastin deposition in the atrium.