Ricerc@Sapienza

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.