Unraveling the epigenetic landscape of pulmonary arterial hypertension: implications for personalized medicine development

Jaydev Dave, Vineeta Jagana, Radoslav Janostiak, Malik Bisserier

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Pulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right heart failure and even death. Multiple biological processes, such as smooth muscle proliferation, endothelial dysfunction, inflammation, and resistance to apoptosis, are associated with PAH. Increasing evidence suggests that epigenetic factors play an important role in PAH by regulating the chromatin structure and altering the expression of critical genes. For example, aberrant DNA methylation and histone modifications such as histone acetylation and methylation have been observed in patients with PAH and are linked to vascular remodeling and pulmonary vascular dysfunction. In this review article, we provide a comprehensive overview of the role of key epigenetic targets in PAH pathogenesis, including DNA methyltransferase (DNMT), ten-eleven translocation enzymes (TET), switch-independent 3A (SIN3A), enhancer of zeste homolog 2 (EZH2), histone deacetylase (HDAC), and bromodomain-containing protein 4 (BRD4). Finally, we discuss the potential of multi-omics integration to better understand the molecular signature and profile of PAH patients and how this approach can help identify personalized treatment approaches.

Original languageEnglish
Article number477
JournalJournal of Translational Medicine
Volume21
Issue number1
DOIs
StatePublished - Dec 2023
Externally publishedYes

Keywords

  • Epidrugs
  • Epigenetic
  • PAH
  • Pulmonary arterial hypertension
  • Treatment

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