Epigenetic mechanisms, including DNA methylation and
histone post-translational modifications (PTMs), have been known to regulate
chromatin structure and lineage-specific gene expression during cardiovascular development and disease. However, alterations in the landscape of
histone PTMs and their contribution to the pathogenesis of incurable
cardiovascular diseases such as
pulmonary hypertension (PH) and associated right
heart failure (RHF) remain largely unexplored. This review focusses on the studies in PH and RHF that investigated the gene families that write (
histone acetyltransferases), read (
bromodomain-containing proteins) or erase (
histone deacetylases [HDACs] and
sirtuins [
SIRT]) acetyl moieties from the ε-amino group of
lysine residues of
histones and non-
histone proteins. Analysis of cells and tissues isolated from the in vivo preclinical models of PH and human
pulmonary arterial hypertension not only confirmed significant alterations in the expression levels of multiple HDACs,
SIRT1,
SIRT3 and BRD4
proteins but also demonstrated their strong association to proliferative, inflammatory and fibrotic phenotypes linked to the pathological vascular remodelling process. Due to the reversible nature of post-translational
protein acetylation, the therapeutic efficacy of numerous small-molecule inhibitors (
vorinostat,
valproic acid,
sodium butyrate,
mocetinostat,
entinostat,
tubastatin A,
apabetalone, JQ1 and
resveratrol) have been evaluated in different preclinical models of
cardiovascular disease, which revealed the promising therapeutic benefits of targeting
histone acetylation pathways in the attenuation of
cardiac hypertrophy,
fibrosis, left heart dysfunction, PH and RHF. This review also emphasizes the need for deeper molecular insights into the contribution of epigenetic changes to PH pathogenesis and therapeutic evaluation of
isoform-specific modulation in ex vivo and in vivo models of PH and RHF. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.