Integrating epigenetics and metabolomics to advance treatments for pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a devastating vascular disease with multiple etiologies. Emerging evidence supports a fundamental role for epigenetic machinery and metabolism in the initiation and progression of PAH. Here, we summarize emerging epigenetic mechanisms that have been identified as contributors to PAH evolution, specifically, DNA methylation, histone modifications, and microRNAs. Furthermore, the interplay between epigenetics with metabolism is explored while new crosstalk targets to be investigated in PAH are proposed that highlight multi-omics strategies including integrated epigenomics and metabolomics. Therapeutic opportunities and challenges associated with epigenetics and metabolomics in PAH are examined, highlighting the role that epigenetics and metabolomics have in facilitating early detection, personalized dietary plans, and advanced drug therapy for PAH.