Regenerative responses after mild heart injuries for cardiomyocyte proliferation in zebrafish

Dev Dyn. 2014 Nov;243(11):1477-86. doi: 10.1002/dvdy.24171. Epub 2014 Aug 19.

Abstract

Background: The zebrafish heart regenerates after various severe injuries. Common processes of heart regeneration are cardiomyocyte proliferation, activation of epicardial tissue, and neovascularization. In order to further characterize heart regeneration processes, we introduced milder injuries and compared responses to those induced by ventricular apex resection, a widely used injury method. We used scratching of the ventricular surface and puncturing of the ventricle with a fine tungsten needle as injury-inducing techniques.

Results: Scratching the ventricular surface induced subtle cardiomyocyte proliferation and responses of the epicardium. Endothelial cell accumulation was limited to the surface of the heart. Ventricular puncture induced cardiomyocyte proliferation, endocardial and epicardial activation, and neo-vascularization, similar to the resection method. However, the degree of the responses was milder, correlating with milder injury. Sham operation induced epicardial aldh1a2 expression but not tbx18 and WT1.

Conclusions: Puncturing the ventricle induces responses equivalent to resection at milder degrees in a shorter time frame and can be used as a simple injury model. Scratching the ventricle did not induce heart regeneration and can be used for studying wound responses to epicardium.

Keywords: cardiomyocytes; endothelial cells; epicardial cells; heart; regeneration; zebrafish.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / physiology*
  • Endothelial Cells / metabolism
  • Heart Injuries / physiopathology*
  • Heart Ventricles / physiopathology*
  • Heart Ventricles / surgery
  • Histological Techniques
  • Image Processing, Computer-Assisted
  • In Situ Hybridization
  • Myocytes, Cardiac / physiology*
  • Regeneration / physiology*
  • Retinal Dehydrogenase / metabolism
  • T-Box Domain Proteins / metabolism
  • WT1 Proteins / metabolism
  • Wound Healing / physiology
  • Zebrafish / physiology*
  • Zebrafish Proteins / metabolism

Substances

  • T-Box Domain Proteins
  • WT1 Proteins
  • Zebrafish Proteins
  • tbx18 protein, zebrafish
  • Retinal Dehydrogenase