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

Davide Bonvissuto, Marcello Ceci, Carol Lauri, Veronica Volpe, Roberte Bertone, Davide Cervia, Claudio Sette, Rosalba Gornati, Nicla Romano

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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 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.
Lingua originaleEnglish
pagine (da-a)166471-N/A
RivistaBIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE
Volume1868
DOI
Stato di pubblicazionePubblicato - 2022

Keywords

  • Animals
  • Blebbistatin
  • Cardiac hyperplasy
  • Cardiac hypertrophy
  • Cardiomegaly
  • Ex vivo model
  • Heterocyclic Compounds, 4 or More Rings
  • Humans
  • Pericardium
  • Phenylephrine
  • Zebrafish

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