Can Blebbistatin block the hypertrophy status in the zebrafish ex vivo cardiac model?

Autor: Bonvissuto D; Department of Neuroscience, Section of Human Anatomy, University of Sacred Heart, Rome, Italy., Ceci M; Department of Ecological and Biological Sciences, Tuscia University, Viterbo, Italy., Lauri C; Department of Ecological and Biological Sciences, Tuscia University, Viterbo, Italy., Volpe V; Department of Ecological and Biological Sciences, Tuscia University, Viterbo, Italy., Bertone R; Department of Ecological and Biological Sciences, Tuscia University, Viterbo, Italy., Cervia D; Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo, Italy., Sette C; Department of Neuroscience, Section of Human Anatomy, University of Sacred Heart, Rome, Italy; GSTEP-Organoids Research Core Facility, IRCCS Fondazione Policlinico A. Gemelli, Rome, Italy., Gornati R; Department of Biotechnologies and Life Sciences, Insubria University, Varese, Italy., Romano N; Department of Ecological and Biological Sciences, Tuscia University, Viterbo, Italy. Electronic address: nromano@unitus.it.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2022 Oct 01; Vol. 1868 (10), pp. 166471. Date of Electronic Publication: 2022 Jun 21.
DOI: 10.1016/j.bbadis.2022.166471
Abstrakt: 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 500 μM 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.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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