{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:23:43Z","timestamp":1777580623434,"version":"3.51.4"},"reference-count":211,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["NHS2015T066"],"award-info":[{"award-number":["NHS2015T066"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BIM-MEC\/4578\/2014"],"award-info":[{"award-number":["PTDC\/BIM-MEC\/4578\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Cardiovascular Alliance (DCVA)","award":["PHAEDRA IMPACT Consortium"],"award-info":[{"award-number":["PHAEDRA IMPACT Consortium"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary artery hypertension (PAH) is a rare chronic disease with high impact on patients\u2019 quality of life and currently no available cure. PAH is characterized by constant remodeling of the pulmonary artery by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), fibroblasts (FBs) and endothelial cells (ECs). This remodeling eventually leads to increased pressure in the right ventricle (RV) and subsequent right ventricle hypertrophy (RVH) which, when left untreated, progresses into right ventricle failure (RVF). PAH can not only originate from heritable mutations, but also develop as a consequence of congenital heart disease, exposure to drugs or toxins, HIV, connective tissue disease or be idiopathic. While much attention was drawn into investigating and developing therapies related to the most well understood signaling pathways in PAH, in the last decade, a shift towards understanding the epigenetic mechanisms driving the disease occurred. In this review, we reflect on the different epigenetic regulatory factors that are associated with the pathology of RV remodeling, and on their relevance towards a better understanding of the disease and subsequently, the development of new and more efficient therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms21238901","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T09:06:28Z","timestamp":1606208788000},"page":"8901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities?"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-4771","authenticated-orcid":false,"given":"Jordy M. M.","family":"Kocken","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Faculty of Sciences and Engineering, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"}]},{"given":"Paula A.","family":"da Costa Martins","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Faculty of Sciences and Engineering, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Unidade de Investiga\u00e7\u00e3o Cardiovascular, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"37","author":"Humbert","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S2213-2600(15)00544-5","article-title":"BMPR2 mutations and survival in pulmonary arterial hypertension: An individual participant data meta-analysis","volume":"4","author":"Evans","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lan, N.S.H., Massam, B.D., Kulkarni, S.S., and Lang, C.C. (2018). Pulmonary Arterial Hypertension: Pathophysiology and Treatment. Diseases, 6.","DOI":"10.3390\/diseases6020038"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ccl.2016.04.001","article-title":"World Health Organization Group I Pulmonary Hypertension: Epidemiology and Pathophysiology","volume":"34","author":"Prins","year":"2016","journal-title":"Cardiol. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e003973","DOI":"10.1161\/CIRCOUTCOMES.117.003973","article-title":"Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension","volume":"11","author":"Wijeratne","year":"2018","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3924517","DOI":"10.1155\/2018\/3924517","article-title":"Health-Related Quality of Life in Pulmonary Hypertension and Its Clinical Correlates: A Cross-Sectional Study","volume":"2018","author":"Reis","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sikirica, M., Iorga, S.R., Bancroft, T., and Potash, J. (2014). The economic burden of pulmonary arterial hypertension (PAH) in the US on payers and patients. BMC Health Serv. Res., 14.","DOI":"10.1186\/s12913-014-0676-0"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1161\/CIRCULATIONAHA.114.006971","article-title":"Clinical Diagnosis of Pulmonary Hypertension","volume":"130","author":"Rich","year":"2014","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrcardio.2014.191","article-title":"Early detection of pulmonary arterial hypertension","volume":"12","author":"Lau","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F1000","DOI":"10.12688\/f1000research.18811.1","article-title":"The 6th World Symposium on Pulmonary Hypertension: What\u2019s old is new","volume":"8","author":"Condon","year":"2019","journal-title":"F1000Research"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1801899","DOI":"10.1183\/13993003.01899-2018","article-title":"Genetics and genomics of pulmonary arterial hypertension","volume":"53","author":"Morrell","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S0002-9440(10)61705-1","article-title":"Plexiform lesion in severe pulmonary hypertension: Association with glomeruloid lesion","volume":"159","author":"Tuder","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"L548","DOI":"10.1152\/ajplung.00428.2006","article-title":"Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension","volume":"293","author":"Masri","year":"2007","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1172\/JCI1910","article-title":"Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension","volume":"101","author":"Lee","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1161\/01.CIR.0000012754.72951.3D","article-title":"Primary Pulmonary Hypertension Is Associated with Reduced Pulmonary Vascular Expression of Type II Bone Morphogenetic Protein Receptor","volume":"105","author":"Atkinson","year":"2002","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e91327","DOI":"10.1172\/jci.insight.91327","article-title":"Discerning functional hierarchies of microRNAs in pulmonary hypertension","volume":"2","author":"Negi","year":"2017","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"37641","DOI":"10.1074\/jbc.M110.132415","article-title":"Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type II","volume":"285","author":"Durrington","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1161\/ATVBAHA.113.302054","article-title":"Downregulation of bone morphogenetic protein receptor axis during HIV-1 and cocaine-mediated pulmonary smooth muscle hyperplasia: Implications for HIV-related pulmonary arterial hypertension","volume":"33","author":"Dalvi","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1164\/rccm.200712-1807OC","article-title":"Clinical Outcomes of Pulmonary Arterial Hypertension in Carriers of BMPR2 Mutation","volume":"177","author":"Sztrymf","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1161\/CIRCULATIONAHA.105.601930","article-title":"Relationship of BMPR2 Mutations to Vasoreactivity in Pulmonary Arterial Hypertension","volume":"113","author":"Elliott","year":"2006","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1700740","DOI":"10.1183\/13993003.00740-2017","article-title":"Mortality in pulmonary arterial hypertension: Prediction by the 2015 European pulmonary hypertension guidelines risk stratification model","volume":"50","author":"Hoeper","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1183\/09031936.00078411","article-title":"ASPIRE registry: Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre","volume":"39","author":"Hurdman","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1164\/rccm.201305-0898ED","article-title":"Death in pulmonary arterial hypertension","volume":"188","author":"Oudiz","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D4","DOI":"10.1016\/j.jacc.2013.10.025","article-title":"Relevant issues in the pathology and pathobiology of pulmonary hypertension","volume":"62","author":"Tuder","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1056\/NEJM199507273330403","article-title":"Reduced Expression of Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension","volume":"333","author":"Giaid","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1172\/JCI3862","article-title":"The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia","volume":"103","author":"Fagan","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25130","DOI":"10.1074\/jbc.274.35.25130","article-title":"Vascular Endothelial Growth Factor Signals Endothelial Cell Production of Nitric Oxide and Prostacyclin through Flk-1\/KDR Activation of c-Src","volume":"274","author":"He","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.drudis.2018.12.001","article-title":"TGF\u03b2 and BMPRII signalling pathways in the pathogenesis of pulmonary arterial hypertension","volume":"24","author":"Tielemans","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7265487","DOI":"10.1155\/2020\/7265487","article-title":"Novel Molecular Mechanisms of Pulmonary Hypertension: A Search for Biomarkers and Novel Drug Targets\u2014From Bench to Bed Site","volume":"2020","author":"Gajecki","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/S0006-291X(88)81362-7","article-title":"L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation","volume":"153","author":"Palmer","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","first-page":"239","article-title":"The nitric oxide-cyclic GMP signal transduction system for intracellular and intercellular communication","volume":"49","author":"Murad","year":"1994","journal-title":"Recent. Prog. Horm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lehners, M., Dobrowinski, H., Feil, S., and Feil, R. (2018). cGMP Signaling and Vascular Smooth Muscle Cell Plasticity. J. Cardiovasc. Dev. Dis., 5.","DOI":"10.3390\/jcdd5020020"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1056\/NEJM199512143332416","article-title":"Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension","volume":"333","author":"Xue","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/pupt.2001.0311","article-title":"Inhaled Nitric Oxide and Methemoglobin in Full-Term Infants with Persistent Pulmonary Hypertension of the Newborn","volume":"15","author":"Salguero","year":"2002","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.vph.2012.09.001","article-title":"Cyclic guanosine monophosphate signalling pathway in pulmonary arterial hypertension","volume":"58","author":"Chen","year":"2013","journal-title":"Vasc. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1378\/chest.125.2.580","article-title":"Hemodynamic Response to Sildenafil, Nitric Oxide, and Iloprost in Primary Pulmonary Hypertension","volume":"125","author":"Leuchte","year":"2004","journal-title":"Chest"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"528783","DOI":"10.1155\/2014\/528783","article-title":"Effect of PAH specific therapy on pulmonary hemodynamics and six-minute walk distance in portopulmonary hypertension: A systematic review and meta-analysis","volume":"2014","author":"Faisal","year":"2014","journal-title":"Pulm. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1183\/16000617.0067-2015","article-title":"Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension","volume":"24","author":"Lang","year":"2015","journal-title":"Eur. Respir. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1165\/ajrcmb.26.2.4695","article-title":"Differential Effects of Stable Prostacyclin Analogs on Smooth Muscle Proliferation and Cyclic AMP Generation in Human Pulmonary Artery","volume":"26","author":"Clapp","year":"2002","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.yjmcc.2010.10.010","article-title":"PKA and Epac synergistically inhibit smooth muscle cell proliferation","volume":"50","author":"Hewer","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_42","first-page":"A1804","article-title":"Decreased Expression and Activity of Epac (Exchange Protein Directly Activated by cAMP) in Pulmonary Arterial Hypertension","volume":"201","author":"Murray","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_43","first-page":"CD012785","article-title":"Prostacyclin for pulmonary arterial hypertension","volume":"5","author":"Barnes","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.2174\/092986706777441968","article-title":"Endothelin-1: The Yin and Yang on Vascular Function","volume":"13","author":"Flora","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1093\/cvr\/28.11.1613","article-title":"Why are circulating concentrations of endothelin-1 so low?","volume":"28","author":"Frelin","year":"1994","journal-title":"Cardiovasc. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0163-7258(96)00101-5","article-title":"The endothelin system and its potential as a therapeutic target in cardiovascular disease","volume":"72","author":"Gray","year":"1996","journal-title":"Pharmacol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1096\/fasebj.9.12.7672512","article-title":"Endothelin receptors and calcium signaling","volume":"9","author":"Pollock","year":"1995","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/bs.apha.2016.06.002","article-title":"Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders","volume":"78","author":"Ringvold","year":"2017","journal-title":"Adv. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1172\/JCI116338","article-title":"Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells","volume":"91","author":"Hirata","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.cjca.2012.05.013","article-title":"Hemodynamic Stability after Transitioning between Endothelin Receptor Antagonists in Patients with Pulmonary Arterial Hypertension","volume":"29","author":"Fox","year":"2013","journal-title":"Can. J. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"701","DOI":"10.3904\/kjim.2013.28.6.701","article-title":"Meta-analysis of randomized controlled trials of bosentan for treatment of pulmonary arterial hypertension","volume":"28","author":"Lee","year":"2013","journal-title":"Korean J. Intern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa012212","article-title":"Bosentan Therapy for Pulmonary Arterial Hypertension","volume":"346","author":"Rubin","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1213917","article-title":"Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension","volume":"369","author":"Pulido","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1161\/CIRCULATIONAHA.107.742510","article-title":"Ambrisentan for the Treatment of Pulmonary Arterial Hypertension","volume":"117","author":"Olschewski","year":"2008","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1046\/j.1523-1747.2001.01256.x","article-title":"Fibroblast Matrix Gene Expression and Connective Tissue Remodeling: Role of Endothelin-1","volume":"116","author":"Xu","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.amjcard.2011.03.066","article-title":"Prevalence and Impact of Coronary Artery Disease in Patients with Pulmonary Arterial Hypertension","volume":"108","author":"Shimony","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/micc.12247","article-title":"Right Ventricular Angiogenesis is an Early Adaptive Response to Chronic Hypoxia-Induced Pulmonary Hypertension","volume":"22","author":"Kolb","year":"2015","journal-title":"Microcirculation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"0910161","DOI":"10.1115\/1.4044174","article-title":"Interactions between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension","volume":"141","author":"Avazmohammadi","year":"2019","journal-title":"J. Biomech. Eng."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1161\/CIRCULATIONAHA.114.012975","article-title":"Molecular Mechanisms of Right Ventricular Failure","volume":"132","author":"Reddy","year":"2015","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1038\/mt.2012.145","article-title":"AAV9-mediated VEGF-B Gene Transfer Improves Systolic Function in Progressive Left Ventricular Hypertrophy","volume":"20","author":"Huusko","year":"2012","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s00059-019-4815-6","article-title":"Right ventricular function in pulmonary (arterial) hypertension","volume":"44","author":"Tello","year":"2019","journal-title":"Herz"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1161\/01.CIR.102.4.470","article-title":"Left Ventricular Hypertrophy","volume":"102","author":"Lorell","year":"2000","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.yexcr.2017.03.052","article-title":"The role of cardiac energy metabolism in cardiac hypertrophy and failure","volume":"360","author":"Tuomainen","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1006\/jmcc.1997.0429","article-title":"Energy metabolism in normal and hypertrophied right ventricle of the ferret heart","volume":"29","author":"Do","year":"1997","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1161\/01.HYP.0000144292.69599.0c","article-title":"Mechanisms for Increased Glycolysis in the Hypertrophied Rat Heart","volume":"44","author":"Nascimben","year":"2004","journal-title":"Hypertension"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s00109-010-0679-1","article-title":"Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure","volume":"88","author":"Piao","year":"2010","journal-title":"J. Mol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"188","DOI":"10.4093\/dmj.2015.39.3.188","article-title":"Pyruvate Dehydrogenase Kinases: Therapeutic Targets for Diabetes and Cancers","volume":"39","author":"Jeoung","year":"2015","journal-title":"Diabetes Metab. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.bbamcr.2010.08.006","article-title":"Hypoxia-inducible factor 1: Regulator of mitochondrial metabolism and mediator of ischemic preconditioning","volume":"1813","author":"Semenza","year":"2011","journal-title":"Biochimica. Biophysica. Acta."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.cardiores.2007.05.012","article-title":"Right-ventricular failure is associated with increased mitochondrial complex II activity and production of reactive oxygen species","volume":"75","author":"Redout","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"326","DOI":"10.21037\/atm.2017.06.27","article-title":"The role of reactive oxygen species in the pathophysiology of cardiovascular diseases and the clinical significance of myocardial redox","volume":"5","author":"Moris","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.lfs.2017.02.016","article-title":"LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats","volume":"174","author":"Zhu","year":"2017","journal-title":"Life Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"H224","DOI":"10.1152\/ajpheart.00507.2018","article-title":"Reversal of right ventricular failure by chronic alpha1A-subtype adrenergic agonist therapy","volume":"316","author":"Cowley","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Power, A.S., Norman, R., Jones, T.L.M., Hickey, A.J., and Ward, M.L. (2019). Mitochondrial function remains impaired in the hypertrophied right ventricle of pulmonary hypertensive rats following short duration metoprolol treatment. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214740"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCHEARTFAILURE.111.966127","article-title":"Metabolic Gene Remodeling and Mitochondrial Dysfunction in Failing Right Ventricular Hypertrophy Secondary to Pulmonary Arterial Hypertension","volume":"6","author":"Mizuno","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0008-6363(00)00197-8","article-title":"Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury","volume":"49","author":"Tsutsui","year":"2001","journal-title":"Cardiovasc. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1161\/CIRCRESAHA.117.311401","article-title":"Reactive Oxygen Species in Metabolic and Inflammatory Signaling","volume":"122","author":"Forrester","year":"2018","journal-title":"Circ. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1253\/circj.CJ-13-1586","article-title":"Role of Endothelial Nitric Oxide Synthase and Collagen Metabolism in Right Ventricular Remodeling due to Pulmonary Hypertension","volume":"78","author":"Nergui","year":"2014","journal-title":"Circ. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1093\/eurjhf\/hfq066","article-title":"Early inflammatory response during the development of right ventricular heart failure in a rat model","volume":"12","author":"Campian","year":"2010","journal-title":"Eur. J. Heart Fail."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/eurheartj\/ehr111","article-title":"Prolonged overcirculation-induced pulmonary arterial hypertension as a cause of right ventricular failure","volume":"33","author":"Rondelet","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1007\/s004240100612","article-title":"Endotoxin and cytokines alter contractile protein expression in cardiac myocytes in vivo","volume":"442","author":"Patten","year":"2001","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"H1813","DOI":"10.1152\/ajpheart.00036.2004","article-title":"In vivo TNF-\u03b1 inhibition ameliorates cardiac mitochondrial dysfunction, oxidative stress, and apoptosis in experimental heart failure","volume":"287","author":"Moe","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"140","DOI":"10.15420\/cfr.2019.15.2","article-title":"Right Ventricular Failure: Pathophysiology, Diagnosis and Treatment","volume":"5","author":"Arrigo","year":"2019","journal-title":"Card. Fail. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1801906","DOI":"10.1183\/13993003.01906-2018","article-title":"Intensive care, right ventricular support and lung transplantation in patients with pulmonary hypertension","volume":"53","author":"Hoeper","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/ije\/dyr184","article-title":"The Epigenotype","volume":"41","author":"Waddington","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"ref_85","unstructured":"Russo, V.E.A., Martienssen, R.A., and Riggs, A.D. (1996). Epigenetic Mechanisms of Gene Regulation, Cold Spring Harbor Laboratory Press."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0092-8674(00)81656-6","article-title":"DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development","volume":"99","author":"Okano","year":"1999","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"aad9780","DOI":"10.1126\/science.aad9780","article-title":"Epigenetic balance of gene expression by Polycomb and COMPASS families","volume":"352","author":"Piunti","year":"2016","journal-title":"Science"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1093\/nar\/gkq147","article-title":"Chromatin methylation activity of Dnmt3a and Dnmt3a\/3L is guided by interaction of the ADD domain with the histone H3 tail","volume":"38","author":"Zhang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9111","DOI":"10.1073\/pnas.1604666113","article-title":"On the origin and evolutionary consequences of gene body DNA methylation","volume":"113","author":"Bewick","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/21541264.2016.1246076","article-title":"H3K36 methylation state and associated silencing mechanisms","volume":"8","author":"Suzuki","year":"2017","journal-title":"Transcription"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.1147939","article-title":"UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells","volume":"317","author":"Bostick","year":"2007","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1101\/gad.220467.113","article-title":"Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation","volume":"27","author":"Rothbart","year":"2013","journal-title":"Genes Dev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nature12750","article-title":"TET enzymes, TDG and the dynamics of DNA demethylation","volume":"502","author":"Kohli","year":"2013","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.1093\/nar\/gks155","article-title":"Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation","volume":"40","author":"Hashimoto","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Otani, J., Kimura, H., Sharif, J., Endo, T.A., Mishima, Y., Kawakami, T., Koseki, H., Shirakawa, M., Suetake, I., and Tajima, S. (2013). Cell cycle-dependent turnover of 5-hydroxymethyl cytosine in mouse embryonic stem cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082961"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature10716","article-title":"DNA-binding factors shape the mouse methylome at distal regulatory regions","volume":"480","author":"Stadler","year":"2011","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1038\/s41467-019-09937-w","article-title":"Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers","volume":"10","author":"Ando","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/jcp.21224","article-title":"DNA methylation: The nuts and bolts of repression","volume":"213","author":"Miranda","year":"2007","journal-title":"J. Cell Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1073\/pnas.51.5.786","article-title":"Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis","volume":"51","author":"Allfrey","year":"1964","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1073\/pnas.95.4.1540","article-title":"Reconstitution of hyperacetylated, DNase I-sensitive chromatin characterized by high conformational flexibility of nucleosomal\u2009DNA","volume":"95","author":"Krajewski","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1002\/j.1460-2075.1994.tb06451.x","article-title":"Core histone hyperacetylation co-maps with generalized DNase I sensitivity in the chicken beta-globin chromosomal domain","volume":"13","author":"Hebbes","year":"1994","journal-title":"EMBO J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/bfgp\/ell028","article-title":"Histone acetylation in gene regulation","volume":"5","author":"Verdone","year":"2006","journal-title":"Brief. Funct. Genom."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1038\/sj.onc.1210619","article-title":"Chemistry of acetyl transfer by histone modifying enzymes: Structure, mechanism and implications for effector design","volume":"26","author":"Hodawadekar","year":"2007","journal-title":"Oncogene"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1021\/bi602513x","article-title":"Catalytic mechanism of a MYST family histone acetyltransferase","volume":"46","author":"Berndsen","year":"2007","journal-title":"Biochemistry"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1021\/cr500452k","article-title":"Protein lysine acetylation by p300\/CBP","volume":"115","author":"Dancy","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_106","first-page":"166","article-title":"Histone deacetylase inhibitors: Molecular mechanisms of action and clinical trials as anti-cancer drugs","volume":"3","author":"Kim","year":"2011","journal-title":"Am. J. Transl. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"a018713","DOI":"10.1101\/cshperspect.a018713","article-title":"Erasers of histone acetylation: The histone deacetylase enzymes","volume":"6","author":"Seto","year":"2014","journal-title":"Cold Spring Harbor Perspect. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"190338","DOI":"10.1098\/rsos.190338","article-title":"N-acetyl lysine derivatives with zinc binding groups as novel HDAC inhibitors","volume":"6","author":"Wang","year":"2019","journal-title":"R. Soc. Open Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev.biochem.73.011303.073651","article-title":"The Sir2 Family of Protein Deacetylases","volume":"73","author":"Blander","year":"2004","journal-title":"Annu. Rev. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.4161\/epi.21975","article-title":"Histone phosphorylation: A chromatin modification involved in diverse nuclear events","volume":"7","author":"Rossetto","year":"2012","journal-title":"Epigenetics"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"26628","DOI":"10.1074\/jbc.M110.215590","article-title":"Phosphorylation of histone H2B serine 32 is linked to cell transformation","volume":"286","author":"Lau","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1158\/0008-5472.CAN-05-0197","article-title":"Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation","volume":"65","author":"Choi","year":"2005","journal-title":"Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/j.biochi.2012.04.018","article-title":"Histone H3 phosphorylation-a versatile chromatin modification for different occasions","volume":"94","author":"Sawicka","year":"2012","journal-title":"Biochimie"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S1097-2765(00)80257-9","article-title":"Phosphorylation of Serine 10 in Histone H3 Is Functionally Linked In Vitro and In Vivo to Gcn5-Mediated Acetylation at Lysine 14","volume":"5","author":"Lo","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S1097-2765(01)00404-X","article-title":"Independent Dynamic Regulation of Histone Phosphorylation and Acetylation during Immediate-Early Gene Induction","volume":"8","author":"Thomson","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S1097-2765(00)80256-7","article-title":"Synergistic Coupling of Histone H3 Phosphorylation and Acetylation in Response to Epidermal Growth Factor Stimulation","volume":"5","author":"Cheung","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/msb.134974","article-title":"The functional diversity of protein lysine methylation","volume":"10","author":"Lanouette","year":"2014","journal-title":"Mol. Syst. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41580-019-0151-1","article-title":"Roles and regulation of histone methylation in animal development","volume":"20","author":"Jambhekar","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/35020506","article-title":"Regulation of chromatin structure by site-specific histone H3 methyltransferases","volume":"406","author":"Rea","year":"2000","journal-title":"Nature"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/ng.154","article-title":"Combinatorial patterns of histone acetylations and methylations in the human genome","volume":"40","author":"Wang","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.immuni.2009.05.006","article-title":"Genome-wide analysis of histone methylation reveals chromatin state-based regulation of gene transcription and function of memory CD8+ T cells","volume":"30","author":"Araki","year":"2009","journal-title":"Immunity"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nrg1882","article-title":"Chromatin remodelling in mammalian differentiation: Lessons from ATP-dependent remodellers","volume":"7","author":"Ohkawa","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0959-437X(00)00175-1","article-title":"Chromatin remodeling in development and differentiation","volume":"11","author":"Leutz","year":"2001","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/oxfordjournals.jbchem.a002834","article-title":"Expression of Chromatin Remodeling Factors during Neural Differentiation","volume":"129","author":"Machida","year":"2001","journal-title":"J. Biochem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1161\/CIRCRESAHA.111.258426","article-title":"Selective class I histone deacetylase inhibition suppresses hypoxia-induced cardiopulmonary remodeling through an antiproliferative mechanism","volume":"110","author":"Cavasin","year":"2012","journal-title":"Circ. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bcp.2014.07.011","article-title":"Dissecting histone deacetylase role in pulmonary arterial smooth muscle cell proliferation and migration","volume":"91","author":"Galletti","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1161\/CIRCULATIONAHA.112.103176","article-title":"Histone deacetylation inhibition in pulmonary hypertension: Therapeutic potential of valproic acid and suberoylanilide hydroxamic acid","volume":"126","author":"Zhao","year":"2012","journal-title":"Circulation"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.freeradbiomed.2016.08.003","article-title":"Inhibition of histone deacetylase reduces transcription of NADPH oxidases and ROS production and ameliorates pulmonary arterial hypertension","volume":"99","author":"Chen","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1161\/HYPERTENSIONAHA.114.04585","article-title":"Megakaryocytic Leukemia 1 Directs a Histone H3 Lysine 4 Methyltransferase Complex to Regulate Hypoxic Pulmonary Hypertension","volume":"65","author":"Chen","year":"2015","journal-title":"Hypertension"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"10460","DOI":"10.1093\/nar\/gku776","article-title":"MRTF-A steers an epigenetic complex to activate endothelin-induced pro-inflammatory transcription in vascular smooth muscle cells","volume":"42","author":"Yang","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1161\/CIRCULATIONAHA.109.916098","article-title":"Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: A basis for excessive cell proliferation and a new therapeutic target","volume":"121","author":"Archer","year":"2010","journal-title":"Circulation"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1097\/HJH.0000000000000309","article-title":"Extrauterine growth restriction on pulmonary vascular endothelial dysfunction in adult male rats: The role of epigenetic mechanisms","volume":"32","author":"Zhang","year":"2014","journal-title":"J. Hypertens."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"612","DOI":"10.4161\/cc.9.3.10612","article-title":"Cardiac ventricular chambers are epigenetically distinguishable","volume":"9","author":"Mathiyalagan","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1164\/rccm.201007-1106OC","article-title":"Suppression of Histone Deacetylases Worsens Right Ventricular Dysfunction after Pulmonary Artery Banding in Rats","volume":"183","author":"Bogaard","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_136","first-page":"138","article-title":"On protein synthesis","volume":"12","author":"Crick","year":"1958","journal-title":"Symp. Soc. Exp. Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature09792","article-title":"Initial impact of the sequencing of the human genome","volume":"470","author":"Lander","year":"2011","journal-title":"Nature"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"537","DOI":"10.2174\/138920210793175895","article-title":"MicroRNA: Biogenesis, Function and Role in Cancer","volume":"11","author":"Macfarlane","year":"2010","journal-title":"Curr. Genom."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.tcb.2019.12.004","article-title":"Biogenesis and Functions of Circular RNAs Come into Focus","volume":"30","author":"Xiao","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"11667","DOI":"10.1073\/pnas.0904715106","article-title":"Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression","volume":"106","author":"Khalil","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1261\/rna.2248605","article-title":"MicroRNA function: Multiple mechanisms for a tiny RNA?","volume":"11","author":"Pillai","year":"2005","journal-title":"RNA N. Y."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-Y","article-title":"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14","volume":"75","author":"Lee","year":"1993","journal-title":"Cell"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1093\/nar\/gki567","article-title":"Clustering and conservation patterns of human microRNAs","volume":"33","author":"Altuvia","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature03049","article-title":"Processing of primary microRNAs by the Microprocessor complex","volume":"432","author":"Denli","year":"2004","journal-title":"Nature"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1126\/science.1178705","article-title":"A high-resolution structure of the pre-microRNA nuclear export machinery","volume":"326","author":"Okada","year":"2009","journal-title":"Science"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1172\/JCI70577","article-title":"Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy","volume":"124","author":"Bang","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nrg3965","article-title":"Towards a molecular understanding of microRNA-mediated gene silencing","volume":"16","author":"Jonas","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"14189","DOI":"10.1038\/s41598-018-32635-4","article-title":"Comprehensive Evolutionary Analysis of the Major RNA-Induced Silencing Complex Members","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1073\/pnas.73.11.3852","article-title":"Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures","volume":"73","author":"Sanger","year":"1976","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/0092-8674(91)90244-S","article-title":"Scrambled exons","volume":"64","author":"Nigro","year":"1991","journal-title":"Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molcel.2014.08.019","article-title":"circRNA Biogenesis Competes with Pre-mRNA Splicing","volume":"56","author":"Meyer","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1177\/1535370217708978","article-title":"Circular RNA \u2013 New member of noncoding RNA with novel functions","volume":"242","author":"Hsiao","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nsmb.2959","article-title":"Exon-intron circular RNAs regulate transcription in the nucleus","volume":"22","author":"Li","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.molcel.2013.08.017","article-title":"Circular Intronic Long Noncoding RNAs","volume":"51","author":"Zhang","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature11993","article-title":"Natural RNA circles function as efficient microRNA sponges","volume":"495","author":"Hansen","year":"2013","journal-title":"Nature"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature11928","article-title":"Circular RNAs are a large class of animal RNAs with regulatory potency","volume":"495","author":"Memczak","year":"2013","journal-title":"Nature"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.molcel.2017.02.017","article-title":"Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis","volume":"66","author":"Legnini","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molcel.2017.02.021","article-title":"Translation of CircRNAs","volume":"66","author":"Pamudurti","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13059-019-1685-4","article-title":"Translation of the circular RNA circ\u03b2-catenin promotes liver cancer cell growth through activation of the Wnt pathway","volume":"20","author":"Liang","year":"2019","journal-title":"Genome Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0092-8674(92)90519-I","article-title":"The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus","volume":"71","author":"Brockdorff","year":"1992","journal-title":"Cell"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0092-8674(92)90520-M","article-title":"The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus","volume":"71","author":"Brown","year":"1992","journal-title":"Cell"},{"key":"ref_162","first-page":"28","article-title":"The product of the H19 gene may function as an RNA","volume":"10","author":"Brannan","year":"1990","journal-title":"Mol. Cell. Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.tig.2014.06.001","article-title":"Transcriptional regulatory functions of nuclear long noncoding RNAs","volume":"30","author":"Vance","year":"2014","journal-title":"Trends Genet."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1101\/gr.078378.108","article-title":"Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation","volume":"18","author":"Dinger","year":"2008","journal-title":"Genome Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.biochi.2011.12.026","article-title":"Roles of long, non-coding RNA in chromosome-wide transcription regulation: Lessons from two dosage compensation systems","volume":"94","author":"Maenner","year":"2012","journal-title":"Biochimie"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"4785","DOI":"10.1007\/s00018-013-1423-0","article-title":"Cell cycle regulation by long non-coding RNAs","volume":"70","author":"Kitagawa","year":"2013","journal-title":"Cell Mol. Life Sci."},{"key":"ref_167","first-page":"992","article-title":"Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging","volume":"6","author":"Grammatikakis","year":"2014","journal-title":"Aging (Albany N. Y.)"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1080\/15476286.2015.1063770","article-title":"Long non-coding RNA and chromatin remodeling","volume":"12","author":"Han","year":"2015","journal-title":"RNA Biol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/bies.201100084","article-title":"Long non-coding RNA modifies chromatin: Epigenetic silencing by long non-coding RNAs","volume":"33","author":"Saxena","year":"2011","journal-title":"BioEssays News Rev. Mol. Cell. Dev. Biol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/nature06992","article-title":"Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription","volume":"454","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1101\/gad.1416106","article-title":"The Evf-2 noncoding RNA is transcribed from the Dlx-5\/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator","volume":"20","author":"Feng","year":"2006","journal-title":"Genes Dev."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.biopha.2017.03.103","article-title":"Long non-coding RNA HOTAIR functions as miRNA sponge to promote the epithelial to mesenchymal transition in esophageal cancer","volume":"90","author":"Xu","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nsmb.2982","article-title":"Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs","volume":"22","author":"Dhir","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1126\/science.1157676","article-title":"Intersection of the RNA interference and X-inactivation pathways","volume":"320","author":"Ogawa","year":"2008","journal-title":"Science"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1100\/tsw.2010.7","article-title":"Long noncoding RNAs, chromatin, and development","volume":"10","author":"Caley","year":"2010","journal-title":"Sci. World J."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nrc.2017.99","article-title":"Non-coding RNA networks in cancer","volume":"18","author":"Anastasiadou","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1093\/eurheartj\/ehx165","article-title":"Non-coding RNAs in cardiovascular diseases: Diagnostic and therapeutic perspectives","volume":"39","author":"Poller","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.jbspin.2016.09.006","article-title":"Long noncoding RNAs in osteoarthritis","volume":"84","author":"Jiang","year":"2017","journal-title":"Joint Bone Spine"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/s12035-012-8359-5","article-title":"Non-coding RNAs in Alzheimer\u2019s Disease","volume":"47","author":"Tan","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1165\/rcmb.2014-0166TR","article-title":"MicroRNAs in pulmonary arterial hypertension","volume":"52","author":"Zhou","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.omtn.2020.05.022","article-title":"Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1\u03b2 and IL-6","volume":"21","author":"Ou","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s12931-020-01444-7","article-title":"In vivo miR-138-5p inhibition alleviates monocrotaline-induced pulmonary hypertension and normalizes pulmonary KCNK3 and SLC45A3 expression","volume":"21","author":"Courboulin","year":"2020","journal-title":"Respir. Res."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/CIRCULATIONAHA.115.020951","article-title":"Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension","volume":"133","author":"Antigny","year":"2016","journal-title":"Circulation"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"117919","DOI":"10.1016\/j.lfs.2020.117919","article-title":"MiR-18a-5p contributes to enhanced proliferation and migration of PASMCs via targeting Notch2 in pulmonary arterial hypertension","volume":"257","author":"Miao","year":"2020","journal-title":"Life Sci."},{"key":"ref_185","first-page":"9014","article-title":"miR-125a-5p inhibits glycolysis by targeting hexokinase-II to improve pulmonary arterial hypertension","volume":"12","author":"Luo","year":"2020","journal-title":"Aging (Albany N. Y.)"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1161\/CIRCRESAHA.112.267591","article-title":"A Role for miR-145 in Pulmonary Arterial Hypertension","volume":"111","author":"Caruso","year":"2012","journal-title":"Circ. Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"955","DOI":"10.3389\/fphys.2018.00955","article-title":"Circulating MicroRNA Markers for Pulmonary Hypertension in Supervised Exercise Intervention and Nightly Oxygen Intervention","volume":"9","author":"Grunig","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.omtn.2019.08.026","article-title":"Circular RNA hsa_circ_0016070 Is Associated with Pulmonary Arterial Hypertension by Promoting PASMC Proliferation. Molecular therapy","volume":"18","author":"Zhou","year":"2019","journal-title":"Nucleic Acids"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"118420","DOI":"10.1016\/j.lfs.2020.118420","article-title":"CircATP2B4 promotes hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells via the miR-223\/ATR axis","volume":"262","author":"Guo","year":"2020","journal-title":"Life Sci."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s12931-018-0956-z","article-title":"LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT1R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension","volume":"19","author":"Su","year":"2018","journal-title":"Respir. Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1002\/jcp.26279","article-title":"LncRNA-TCONS_00034812 in cell proliferation and apoptosis of pulmonary artery smooth muscle cells and its mechanism","volume":"233","author":"Liu","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"108933","DOI":"10.1016\/j.biopha.2019.108933","article-title":"Long non-coding RNA and mRNA profile analysis of metformin to reverse the pulmonary hypertension vascular remodeling induced by monocrotaline","volume":"115","author":"Sun","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/SHK.0000000000001410","article-title":"LncRNA-Ang362 Promotes Pulmonary Arterial Hypertension by Regulating miR-221 and miR-222","volume":"53","author":"Wang","year":"2019","journal-title":"Shock"},{"key":"ref_194","first-page":"871","article-title":"Long non-coding RNA MALAT1 sponges miR-124\u20133p.1\/KLF5 to promote pulmonary vascular remodeling and cell cycle progression of pulmonary artery hypertension","volume":"44","author":"Wang","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s11010-020-03877-6","article-title":"LincRNA-Cox2 promotes pulmonary arterial hypertension by regulating the let-7a-mediated STAT3 signaling pathway","volume":"475","author":"Cheng","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1164\/rccm.201910-2041OC","article-title":"Long Noncoding RNA TYKRIL Plays a Role in Pulmonary Hypertension via the p53-Mediated Regulation of PDGFR\u03b2","volume":"202","author":"Zehendner","year":"2020","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"H377","DOI":"10.1152\/ajpheart.00717.2019","article-title":"LncRNA-SMILR modulates RhoA\/ROCK signaling by targeting miR-141 to regulate vascular remodeling in pulmonary arterial hypertension","volume":"319","author":"Lei","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"13919","DOI":"10.1038\/s41598-018-32154-2","article-title":"Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles","volume":"8","author":"Johnson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1086\/679721","article-title":"Right ventricular long noncoding RNA expression in human heart failure","volume":"5","author":"Guo","year":"2015","journal-title":"Pulm. Circ."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1086\/675981","article-title":"MicroRNAs in right ventricular (dys)function (2013 Grover Conference series)","volume":"4","author":"Thum","year":"2014","journal-title":"Pulm. Circ."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"413","DOI":"10.7150\/ijms.4514","article-title":"MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis","volume":"9","author":"Qin","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_202","first-page":"511","article-title":"MicroRNA-21 is Associated with the Severity of Right Ventricular Dysfunction in Patients with Hypoxia-Induced Pulmonary Hypertension","volume":"34","author":"Chang","year":"2018","journal-title":"Acta. Cardiologica. Sinica."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"H689","DOI":"10.1152\/ajpheart.00264.2016","article-title":"MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416\/hypoxia\/normoxia model of pulmonary arterial hypertension","volume":"311","author":"Joshi","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/ncb2126","article-title":"MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin\/NFAT signalling","volume":"12","author":"Salic","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"ehy566.4929","DOI":"10.1093\/eurheartj\/ehy566.4929","article-title":"Contribution of miR-199b to right ventricular remodelling due to pressure overload","volume":"39","author":"Koop","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Connolly, M., Garfield, B.E., Crosby, A., Morrell, N.W., Wort, S.J., and Kemp, P.R. (2020). miR-1\u20135p targets TGF-\u03b2R1 and is suppressed in the hypertrophying hearts of rats with pulmonary arterial hypertension. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0229409"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1093\/cvr\/cvx153","article-title":"MicroRNAs in right ventricular remodelling","volume":"113","author":"Batkai","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.biopha.2018.07.057","article-title":"Analyses of long non-coding RNA and mRNA profiles in right ventricle myocardium of acute right heart failure in pulmonary arterial hypertension rats","volume":"106","author":"Cao","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/cvr\/cvw078","article-title":"The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy","volume":"111","author":"Liu","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_210","first-page":"PA5040","article-title":"Long Non-coding RNA H19 in Right Ventricular Failure associated with Pulmonary Arterial Hypertension","volume":"54","author":"Omura","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"a015750","DOI":"10.1101\/cshperspect.a015750","article-title":"Heart fields and cardiac morphogenesis","volume":"4","author":"Kelly","year":"2014","journal-title":"Cold Spring Harbor Perspect. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/8901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:36:39Z","timestamp":1760178999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/8901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,24]]},"references-count":211,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21238901"],"URL":"https:\/\/doi.org\/10.3390\/ijms21238901","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,24]]}}}