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

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Item Type:	Article
Title:	The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion
Creators Name:	Wang, J., Panakova, D., Kikuchi, K., Holdway, J.E., Gemberling, M., Burris, J.S., Singh, S.P., Dickson, A.L., Lin, Y.F., Sabeh, M.K., Werdich, A.A., Yelon, D., Macrae, C.A. and Poss, K.D.
Abstract:	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.
Keywords:	Cardiomyocyte, Genetic Ablation, Heart Regeneration, Epicardium, Endocardium, Heart Failure, Animals, Zebrafish
Source:	Development
ISSN:	0950-1991
Publisher:	Company of Biologists
Volume:	138
Number:	16
Page Range:	3421-3430
Date:	August 2011
Official Publication:	https://doi.org/10.1242/dev.068601
PubMed:	View item in PubMed

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