Can Blebbistatin block the hypertrophy status in the zebrafish ex vivo cardiac model?
Author(s)
Date Issued
2022
Type
article
Volume
1868
Issue
10
Abstract
Ex-vivo simple models are powered tools to study cardiac hypertrophy. It is possible to control the activation of
critical genes and thus test the effects of drug therapies before the in vivo tests. A zebrafish cardiac hypertrophy
developed by 500µM Phenylephrine (PE) treatment in ex vivo culture has been demonstrated to activate the essential expression of the embryonal genes. These genes are the same as those described in several previous pieces
of research on hypertrophic pathology in humans. The efficacy of the chemical drug Blebbistatin (BL) on hypertrophy induced ex vivo cultured hearts is studied in this research. BL can inhibit the myosins and the calcium wave
in counteracting the hypertrophy status caused by PE. Samples treated with PE, BL and PE simultaneously, or
pre/post-treatment with BL, have been analysed for the embryonal gene activation concerning the hypertrophy
status. The qRTPCR has shown an inhibitory effect of BL treatments on the microRNAs downregulation with the
consequent low expression of essential embryonal genes. In particular, BL seems to be effective in blocking the
hyperplasia of the epicardium but less effective in myocardium hypertrophy. The model can make it possible to
obtain knowledge on the transduction pathways activated by BL and investigate the potential use of this drug in
treating cardiac hypertrophy in humans.
Additional information
Sviluppo di un modello ex-vivo per valutare l'effetto di farmaci in modelli traslazionali
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BBA_MolecularBasisDisease_2022.pdf
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