title: Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives.
abstract: 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.
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Dept of Lung Development and Remodeling, member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.
authors.forename: Prakash
authors.initials: P
authors.lastname: Chelladurai
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Dept of Lung Development and Remodeling, member of the German Center for Lung Research (DZL), Bad Nauheim, Germany University of Giessen Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Dept of Lung Development and Remodeling, member of the German Center for Lung Research (DZL), Bad Nauheim, Germany University of Giessen Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany soni.pullamsetti@mpi-bn.mpg.de.
authors.forename: Soni Savai
authors.initials: SS
authors.lastname: Pullamsetti
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D062186:Arterial Pressure / Q000187:drug effects / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D010641:Phenotype; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D012307:Risk Factors
chemical_list: D000959:Antihypertensive Agents; D056572:Histone Deacetylase Inhibitors