TY - JOUR T1 - Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives JF - European Respiratory Review JO - EUROPEAN RESPIRATORY REVIEW SP - 135 LP - 140 DO - 10.1183/16000617.0036-2016 VL - 25 IS - 140 AU - Prakash Chelladurai AU - Werner Seeger AU - Soni Savai Pullamsetti Y1 - 2016/06/01 UR - http://err.ersjournals.com/content/25/140/135.abstract N2 - Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date.An epigenetic component is hypothesised in PAH: an overview of the current literature and future perspectives http://ow.ly/7miS3002BYw ER -