The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion.

Published

Journal Article

Natural models of heart regeneration in lower vertebrates such as zebrafish are based on invasive surgeries causing mechanical injuries that are limited in size. Here, we created a genetic cell ablation model in zebrafish that facilitates inducible destruction of a high percentage of cardiomyocytes. Cell-specific depletion of over 60% of the ventricular myocardium triggered signs of cardiac failure that were not observed after partial ventricular resection, including reduced animal exercise tolerance and sudden death in the setting of stressors. Massive myocardial loss activated robust cellular and molecular responses by endocardial, immune, epicardial and vascular cells. Destroyed cardiomyocytes fully regenerated within several days, restoring cardiac anatomy, physiology and performance. Regenerated muscle originated from spared cardiomyocytes that acquired ultrastructural and electrophysiological characteristics of de-differentiation and underwent vigorous proliferation. Our study indicates that genetic depletion of cardiomyocytes, even at levels so extreme as to elicit signs of cardiac failure, can be reversed by natural regenerative capacity in lower vertebrates such as zebrafish.

Full Text

Duke Authors

Cited Authors

  • Wang, J; Panáková, D; Kikuchi, K; Holdway, JE; Gemberling, M; Burris, JS; Singh, SP; Dickson, AL; Lin, Y-F; Sabeh, MK; Werdich, AA; Yelon, D; Macrae, CA; Poss, KD

Published Date

  • August 2011

Published In

Volume / Issue

  • 138 / 16

Start / End Page

  • 3421 - 3430

PubMed ID

  • 21752928

Pubmed Central ID

  • 21752928

Electronic International Standard Serial Number (EISSN)

  • 1477-9129

Digital Object Identifier (DOI)

  • 10.1242/dev.068601

Language

  • eng

Conference Location

  • England