Givinostat reduces adverse cardiac remodeling through regulating fibroblasts activation

Marika Milan, Valentina Pace, Fabio Maiullari, Maila Chirivì, Denisa Baci, Silvia Maiullari, Luca Madaro, Sonia Maccari, Tonino Stati, Giuseppe Marano, Giacomo Frati, Pier Lorenzo Puri, Elena De Falco, Claudia Bearzi, Roberto Rizzi

Research output: Contribution to journalArticle

Abstract

Cardiovascular diseases (CVDs) are a major burden on the healthcare system: indeed, over two million new cases are diagnosed every year worldwide. Unfortunately, important drawbacks for the treatment of these patients derive from our current inability to stop the structural alterations that lead to heart failure, the common endpoint of many CVDs. In this scenario, a better understanding of the role of epigenetics - hereditable changes of chromatin that do not alter the DNA sequence itself - is warranted. To date, hyperacetylation of histones has been reported in hypertension and myocardial infarction, but the use of inhibitors for treating CVDs remains limited. Here, we studied the effect of the histone deacetylase inhibitor Givinostat on a mouse model of acute myocardial infarction. We found that it contributes to decrease endothelial-to-mesenchymal transition and inflammation, reducing cardiac fibrosis and improving heart performance and protecting the blood vessels from apoptosis through the modulatory effect of cardiac fibroblasts on endothelial cells. Therefore, Givinostat may have potential for the treatment of CVDs.
Original languageEnglish
JournalCell Death and Disease
Volume9
Issue number2
DOIs
Publication statusPublished - Jan 25 2018

Keywords

  • Givinostat
  • cardiovascular diseases
  • inflammation

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    Milan, M., Pace, V., Maiullari, F., Chirivì, M., Baci, D., Maiullari, S., Madaro, L., Maccari, S., Stati, T., Marano, G., Frati, G., Puri, P. L., De Falco, E., Bearzi, C., & Rizzi, R. (2018). Givinostat reduces adverse cardiac remodeling through regulating fibroblasts activation. Cell Death and Disease, 9(2). https://doi.org/10.1038/s41419-017-0174-5