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Givinostat reduces adverse cardiac remodeling through regulating fibroblasts activation

Marika Milan1, Valentina Pace1, Fabio Maiullari1,2

  • 1Institute of Cell Biology and Neurobiology (IBCN), National Research Council of Italy (CNR), Monterotondo Scalo, Rome, 00015, Italy.

Cell Death & Disease
|January 27, 2018
PubMed

Insights

Histone deacetylase inhibitor Givinostat reduced cardiac fibrosis and improved heart function in a mouse model of myocardial infarction. This epigenetic therapy shows promise for treating cardiovascular diseases (CVDs).

Area of Science:

  • Cardiovascular Research
  • Epigenetics
  • Pharmacology

Background:

  • Cardiovascular diseases (CVDs) represent a significant global health burden, with heart failure as a common outcome.
  • Current treatments struggle to halt the structural changes leading to heart failure.
  • Epigenetics, particularly histone modifications, plays a role in CVDs, but therapeutic interventions are limited.

Purpose of the Study:

  • To investigate the therapeutic potential of the histone deacetylase inhibitor, Givinostat, in a mouse model of acute myocardial infarction.
  • To elucidate the mechanisms by which Givinostat impacts cardiac tissue and vascular function post-myocardial infarction.

Main Methods:

  • Utilized a mouse model of acute myocardial infarction.
  • Administered the histone deacetylase inhibitor, Givinostat.
  • Assessed changes in endothelial-to-mesenchymal transition, inflammation, cardiac fibrosis, vascular apoptosis, and cardiac performance.

Main Results:

  • Givinostat treatment decreased endothelial-to-mesenchymal transition and inflammation.
  • The drug reduced cardiac fibrosis and improved overall heart performance.
  • Givinostat protected blood vessels from apoptosis via modulation of cardiac fibroblasts on endothelial cells.

Conclusions:

  • Givinostat demonstrates a protective effect in a mouse model of myocardial infarction.
  • The drug's mechanisms involve reducing fibrosis, inflammation, and vascular apoptosis.
  • Givinostat shows potential as a novel therapeutic agent for cardiovascular diseases.

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