Genetic depletion of over 60% of the ventricular myocardium in zebrafish, which elicited signs of cardiac failure, was fully reversed within several days by natural regenerative capacity.
Zebrafish possess a robust natural regenerative capacity capable of fully reversing severe cardiac failure induced by massive genetic depletion of cardiomyocytes.
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.
Wang et al. (2011) studied Cardiac failure. Genetic cell ablation of cardiomyocytes vs. Partial ventricular resection was evaluated on Cardiac regeneration. Genetic depletion of over 60% of the ventricular myocardium in zebrafish, which elicited signs of cardiac failure, was fully reversed within several days by natural regenerative capacity.