{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:31:59Z","timestamp":1792668719847,"version":"4.5.0"},"reference-count":251,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T00:00:00Z","timestamp":1679184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension is a chronic, progressive disorder of the pulmonary vasculature with associated pulmonary and cardiac remodeling. PAH was a uniformly fatal disease until the late 1970s, but with the advent of targeted therapies, the life expectancy of patients with PAH has now considerably improved. Despite these advances, PAH inevitably remains a progressive disease with significant morbidity and mortality. Thus, there is still an unmet need for the development of new drugs and other interventional therapies for the treatment of PAH. One shortcoming of currently approved vasodilator therapies is that they do not target or reverse the underlying pathogenesis of the disease process itself. A large body of evidence has evolved in the past two decades clarifying the role of genetics, dysregulation of growth factors, inflammatory pathways, mitochondrial dysfunction, DNA damage, sex hormones, neurohormonal pathways, and iron deficiency in the pathogenesis of PAH. This review focuses on newer targets and drugs that modify these pathways as well as novel interventional therapies in PAH.<\/jats:p>","DOI":"10.3390\/ijms24065850","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:33:31Z","timestamp":1679286811000},"page":"5850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["New Drugs and Therapies in Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8089-9399","authenticated-orcid":false,"given":"Aangi J.","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Beckmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounica","family":"Vorla","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-4067","authenticated-orcid":false,"given":"Dinesh K.","family":"Kalra","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/art.37838","article-title":"Borderline Mean Pulmonary Artery Pressure in Patients With Systemic Sclerosis: Transpulmonary Gradient Predicts Risk of Developing Pulmonary Hypertension","volume":"65","author":"Valerio","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.21037\/cdt.2017.04.11","article-title":"Pulmonary hypertension: Diagnosis, imaging techniques, and novel therapies","volume":"7","author":"Goldberg","year":"2017","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1161\/CIRCULATIONAHA.105.602565","article-title":"Chronic Thromboembolic Pulmonary Hypertension","volume":"113","author":"Hoeper","year":"2006","journal-title":"Circulation"},{"key":"ref_5","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":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1183\/09031936.00145608","article-title":"Pulmonary arterial pressure during rest and exercise in healthy subjects: A systematic review","volume":"34","author":"Kovacs","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/ejhf.1570","article-title":"Mildly increased pulmonary arterial pressure: A new disease entity or just a marker of poor prognosis?","volume":"21","author":"Kovacs","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1136\/annrheumdis-2011-200546","article-title":"Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: Results from the PHAROS registry","volume":"71","author":"Bae","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1161\/CIRCULATIONAHA.115.020207","article-title":"Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program","volume":"133","author":"Maron","year":"2016","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shah, A.J., Vorla, M., and Kalra, D.K. (2022). Molecular Pathways in Pulmonary Arterial Hypertension. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710001"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"817","DOI":"10.2147\/JEP.S236743","article-title":"Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension","volume":"13","author":"Zolty","year":"2021","journal-title":"J. Exp. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1056\/NEJMra2000348","article-title":"Pulmonary Arterial Hypertension","volume":"385","author":"Hassoun","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/bmb\/ldq013","article-title":"Editor\u2019s Choice","volume":"94","author":"Vetter","year":"2010","journal-title":"Br. Med. Bull."},{"key":"ref_14","first-page":"w14202","article-title":"The pathogenesis of pulmonary hypertension\u2014An update","volume":"145","author":"Huber","year":"2015","journal-title":"Swiss Med. Wkly."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1056\/NEJMra035488","article-title":"Pulmonary Arterial Hypertension","volume":"351","author":"Farber","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1161\/CIRCRESAHA.113.301141","article-title":"Inflammation and Immunity in the Pathogenesis of Pulmonary Arterial Hypertension","volume":"115","author":"Rabinovitch","year":"2014","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"j5492","DOI":"10.1136\/bmj.j5492","article-title":"Pulmonary arterial hypertension: Pathogenesis and clinical management","volume":"360","author":"Thenappan","year":"2018","journal-title":"BMJ"},{"key":"ref_18","first-page":"e202003","article-title":"Pulmonary arterial hypertension: Cellular and molecular changes in the lung","volume":"2020","author":"Maron","year":"2020","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1183\/09059180.00008411","article-title":"Pulmonary hypertension: The science behind the disease spectrum","volume":"21","author":"Wilkins","year":"2012","journal-title":"Eur. Respir. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11418","DOI":"10.1073\/pnas.0610467104","article-title":"The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted","volume":"104","author":"Bonnet","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pupt.2010.09.001","article-title":"Key role of the RhoA\/Rho kinase system in pulmonary hypertension","volume":"24","author":"Connolly","year":"2011","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1253\/circj.CJ-09-0135","article-title":"Evidence for Rho-Kinase Activation in Patients with Pulmonary Arterial Hypertension","volume":"73","author":"Do","year":"2009","journal-title":"Circ. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1164\/rccm.201410-1802OC","article-title":"Sex Affects Bone Morphogenetic Protein Type II Receptor Signaling in Pulmonary Artery Smooth Muscle Cells","volume":"191","author":"Mair","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1161\/CIRCULATIONAHA.106.632208","article-title":"Right Ventricular Function and Failure","volume":"114","author":"Voelkel","year":"2006","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1016\/j.jacc.2004.02.032","article-title":"Diagnosis and differential assessment of pulmonary arterial hypertension","volume":"43","author":"Barst","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1161\/CIRCULATIONAHA.104.488486","article-title":"Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension","volume":"111","author":"Sitbon","year":"2005","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1056\/NEJM199207093270203","article-title":"The Effect of High Doses of Calcium-Channel Blockers on Survival in Primary Pulmonary Hypertension","volume":"327","author":"Rich","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107576","DOI":"10.1016\/j.pharmthera.2020.107576","article-title":"Pulmonary arterial hypertension specific therapy: The old and the new","volume":"214","author":"Zolty","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1183\/09031936.00058409","article-title":"Sitaxentan-induced hepatic failure in two patients with pulmonary arterial hypertension","volume":"34","author":"Lavelle","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1183\/09031936.00091610","article-title":"Sitaxentan-related acute liver failure in a patient with pulmonary arterial hypertension","volume":"37","author":"Lee","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.1038\/jp.2008.161","article-title":"Role of iNO in the modulation of pulmonary vascular resistance","volume":"28","author":"Schreiber","year":"2008","journal-title":"J. Perinatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1007\/s10741-022-10239-5","article-title":"Therapeutic augmentation of NO-sGC-cGMP signalling: Lessons learned from pulmonary arterial hypertension and heart failure","volume":"27","author":"Triposkiadis","year":"2022","journal-title":"Heart Fail. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1161\/CIRCULATIONAHA.110.981738","article-title":"Soluble Guanylate Cyclase as an Emerging Therapeutic Target in Cardiopulmonary Disease","volume":"123","author":"Stasch","year":"2011","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1183\/09031936.00039808","article-title":"First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension","volume":"33","author":"Grimminger","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1001\/jama.2022.4402","article-title":"Diagnosis and Treatment of Pulmonary Arterial Hypertension","volume":"327","author":"Ruopp","year":"2022","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1742-1241.2010.02525.x","article-title":"How has epoprostenol changed the outcome for patients with pulmonary arterial hypertension?","volume":"64","author":"Barst","year":"2010","journal-title":"Int. J. Clin. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/bph.15016","article-title":"Current and future treatments of pulmonary arterial hypertension","volume":"178","author":"Sommer","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1164\/rccm.202004-1411ED","article-title":"Clarifying the Pulmonary Arterial Hypertension Molecular Landscape Using Functional Genetics","volume":"202","author":"Maron","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"305","DOI":"10.4103\/2045-8932.87293","article-title":"The Genetics of Pulmonary Arterial Hypertension in the Post-BMPR2 Era","volume":"1","author":"Fessel","year":"2011","journal-title":"Pulm. Circ."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","unstructured":"Happ\u00e9, C., Kurakula, K., Sun, X.-Q., Bos, D.D.S.G., Rol, N., Guignabert, C., Tu, L., Schalij, I., Wiesmeijer, K.C., and Tura-Ceide, O. (2020). The BMP Receptor 2 in Pulmonary Arterial Hypertension: When and Where the Animal Model Matches the Patient. Cells, 9.","DOI":"10.3390\/cells9061422"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1093\/hmg\/dds073","article-title":"BMPR-II deficiency elicits pro-proliferative and anti-apoptotic responses through the activation of TGF\u03b2-TAK1-MAPK pathways in PAH","volume":"21","author":"Nasim","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1183\/09031936.00183008","article-title":"Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension","volume":"34","author":"Dewachter","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.coph.2021.05.003","article-title":"Promising therapeutic approaches in pulmonary arterial hypertension","volume":"59","author":"Ali","year":"2021","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1602449","DOI":"10.1183\/13993003.02449-2016","article-title":"Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension","volume":"50","author":"Spiekerkoetter","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1152\/japplphysiol.00595.2005","article-title":"Dominant negative mutation of the TGF-\u03b2 receptor blocks hypoxia-induced pulmonary vascular remodeling","volume":"100","author":"Chen","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1161\/CIRCRESAHA.111.300483","article-title":"Chloroquine Prevents Progression of Experimental Pulmonary Hypertension via Inhibition of Autophagy and Lysosomal Bone Morphogenetic Protein Type II Receptor Degradation","volume":"112","author":"Long","year":"2013","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"L363","DOI":"10.1152\/ajplung.00212.2011","article-title":"The monocrotaline model of pulmonary hypertension in perspective","volume":"302","author":"Farkas","year":"2012","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1165\/rcmb.2013-0100OC","article-title":"Correction of Nonsense BMPR2 and SMAD9 Mutations by Ataluren in Pulmonary Arterial Hypertension","volume":"49","author":"Drake","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12353","DOI":"10.1073\/pnas.1615548113","article-title":"Proposing a mechanism of action for ataluren","volume":"113","author":"Siddiqui","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1183\/09031936.05.00112105","article-title":"Pulmonary arterial hypertension: An autoimmune disease?","volume":"26","author":"Mouthon","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1136\/ard.62.11.1088","article-title":"Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: Application of a registry approach","volume":"62","author":"Mukerjee","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1183\/09031936.05.00045705","article-title":"Autoimmunity and pulmonary hypertension: A perspective","volume":"26","author":"Nicolls","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1164\/rccm.201201-0164OC","article-title":"Modern Age Pathology of Pulmonary Arterial Hypertension","volume":"186","author":"Stacher","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/jcp.1041630104","article-title":"Reciprocal induction of tumor necrosis factor-? and interleukin-? activity mediates fibronectin synthesis in coronary artery smooth muscle cells","volume":"163","author":"Molossi","year":"1995","journal-title":"J. Cell. Physiol."},{"key":"ref_58","first-page":"1349","article-title":"Tenascin-C, proliferation and subendothelial fibronectin in progressive pulmonary vascular disease","volume":"150","author":"Jones","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1164\/rccm.200707-1015OC","article-title":"Identification of Target Antigens of Antifibroblast Antibodies in Pulmonary Arterial Hypertension","volume":"177","author":"Terrier","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"L604","DOI":"10.1152\/ajplung.00309.2011","article-title":"BMP type II receptor deficiency confers resistance to growth inhibition by TGF-\u03b2 in pulmonary artery smooth muscle cells: Role of proinflammatory cytokines","volume":"302","author":"Davies","year":"2012","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"684657","DOI":"10.3389\/fimmu.2021.684657","article-title":"The Role of Regulatory T Cells in Pulmonary Arterial Hypertension","volume":"12","author":"Tian","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"572S","DOI":"10.1378\/chest.128.6_suppl.572S-a","article-title":"Interleukin-6 Causes Mild Pulmonary Hypertension and Augments Hypoxia-Induced Pulmonary Hypertension in Mice","volume":"128","author":"Golembeski","year":"2005","journal-title":"Chest"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1465-9921-10-6","article-title":"Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice","volume":"10","author":"Savale","year":"2009","journal-title":"Respir. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s00380-009-1215-5","article-title":"The efficacy of tocilizumab in a patient with pulmonary arterial hypertension associated with Castleman\u2019s disease","volume":"25","author":"Arita","year":"2010","journal-title":"Heart Vessel."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s12185-009-0346-x","article-title":"Tocilizumab is effective for pulmonary hypertension associated with multicentric Castleman\u2019s disease","volume":"90","author":"Taniguchi","year":"2009","journal-title":"Int. J. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/1756-185X.12324","article-title":"A novel therapeutic approach in pulmonary arterial hypertension as a complication of adult-onset Still\u2019s disease: Targeting IL-6","volume":"17","author":"Kadavath","year":"2014","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2002463","DOI":"10.1183\/13993003.02463-2020","article-title":"Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension","volume":"59","author":"Toshner","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"256","DOI":"10.2353\/ajpath.2008.070395","article-title":"Evidence of a Role for Osteoprotegerin in the Pathogenesis of Pulmonary Arterial Hypertension","volume":"172","author":"Lawrie","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1165\/ajrcmb.11.6.7946395","article-title":"Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline","volume":"11","author":"Voelkel","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1749-6632.1994.tb39794.x","article-title":"Interleukin-1 Receptor Antagonist Inhibits Pulmonary Hypertension Induced by Inflammationa","volume":"725","author":"Voelkel","year":"1994","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_71","first-page":"537613","article-title":"Pulmonary Arterial Hypertension in Adult-Onset Still\u2019s Disease: Rapid Response to Anakinra","volume":"2012","author":"Campos","year":"2012","journal-title":"Case Rep. Rheumatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1164\/rccm.201809-1631LE","article-title":"IL-1 Blockade Reduces Inflammation in Pulmonary Arterial Hypertension and Right Ventricular Failure: A Single-Arm, Open-Label, Phase IB\/II Pilot Study","volume":"199","author":"Trankle","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"L39","DOI":"10.1152\/ajplung.2001.280.1.L39","article-title":"Overexpression of tumor necrosis factor-\u03b1 produces an increase in lung volumes and pulmonary hypertension","volume":"280","author":"Fujita","year":"2001","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/CIRCULATIONAHA.109.933762","article-title":"Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension","volume":"122","author":"Soon","year":"2010","journal-title":"Circulation"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1046\/j.1440-1843.2003.00491.x","article-title":"Effects of IL-1beta, TNF-alpha, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells","volume":"8","author":"Itoh","year":"2003","journal-title":"Respirology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1152\/jappl.1994.77.6.2817","article-title":"TNF potentiates PAF-induced pulmonary vasoconstriction in the rat: Role of neutrophils and thromboxane A2","volume":"77","author":"Chang","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.vph.2012.07.006","article-title":"Monocrotaline-induced pulmonary arterial hypertension is attenuated by TNF-\u03b1 antagonists via the suppression of TNF-\u03b1 expression and NF-\u03baB pathway in rats","volume":"58","author":"Wang","year":"2013","journal-title":"Vasc. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14079","DOI":"10.1038\/ncomms14079","article-title":"TNF\u03b1 drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling","volume":"8","author":"Hurst","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1089\/jir.2006.26.661","article-title":"Etanercept Reduces Late Endotoxin-Induced Pulmonary Hypertension in the Pig","volume":"26","author":"Mutschler","year":"2006","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/1756-185X.12304","article-title":"Preventive and remedial application of etanercept attenuate monocrotaline-induced pulmonary arterial hypertension","volume":"19","author":"Zhang","year":"2019","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2016.12.012","article-title":"30 Years of NF-\u03baB: A Blossoming of Relevance to Human Pathobiology","volume":"168","author":"Zhang","year":"2017","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1378\/chest.06-2243","article-title":"A Nuclear Factor-\u03baB Inhibitor Pyrrolidine Dithiocarbamate Ameliorates Pulmonary Hypertension in Rats","volume":"132","author":"Sawada","year":"2007","journal-title":"Chest"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Price, L.C., Caramori, G., Perros, F., Meng, C., Gambaryan, N., Dorfmuller, P., Montani, D., Casolari, P., Zhu, J., and Dimopoulos, K. (2013). Nuclear Factor \u03ba-B Is Activated in the Pulmonary Vessels of Patients with End-Stage Idiopathic Pulmonary Arterial Hypertension. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075415"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"35764","DOI":"10.1074\/jbc.M607160200","article-title":"Triterpenoid CDDO-Me Blocks the NF-\u03baB Pathway by Direct Inhibition of IKK\u03b2 on Cys-179","volume":"281","author":"Ahmad","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_85","first-page":"435","article-title":"Future Perspectives of Pulmonary Hypertension Treatment","volume":"38","author":"Hsu","year":"2022","journal-title":"Acta Cardiol. Sin."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"41605","DOI":"10.1038\/srep41605","article-title":"Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways","volume":"7","author":"Grzegorzewska","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1177\/23971983211016196","article-title":"A pilot study of dimethyl fumarate in pulmonary arterial hypertension associated with systemic sclerosis","volume":"6","author":"Kong","year":"2021","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1164\/rccm.202009-3481OC","article-title":"Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis\u2013associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial","volume":"204","author":"Zamanian","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"163","DOI":"10.31083\/j.rcm.2020.02.597","article-title":"Current and emerging therapeutic approaches to pulmonary hypertension","volume":"21","author":"Bisserier","year":"2020","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"20458940211057071","DOI":"10.1177\/20458940211057071","article-title":"TORREY, a Phase 2 study to evaluate the efficacy and safety of inhaled seralutinib for the treatment of pulmonary arterial hypertension","volume":"11","author":"Frantz","year":"2021","journal-title":"Pulm. Circ."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1161\/CIRCULATIONAHA.108.779751","article-title":"Combined Tyrosine and Serine\/Threonine Kinase Inhibition by Sorafenib Prevents Progression of Experimental Pulmonary Hypertension and Myocardial Remodeling","volume":"118","author":"Klein","year":"2008","journal-title":"Circulation"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pupt.2017.03.009","article-title":"Sorafenib as a potential strategy for refractory pulmonary arterial hypertension","volume":"44","author":"Kimura","year":"2017","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"121792","DOI":"10.1016\/j.ijpharm.2022.121792","article-title":"Comprehensive review on novel targets and emerging therapeutic modalities for pulmonary arterial Hypertension","volume":"621","author":"Dhoble","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Veeroju, S., Kojonazarov, B., Weiss, A., Ghofrani, H.A., Weissmann, N., Grimminger, F., Seeger, W., Novoyatleva, T., and Schermuly, R.T. (2021). Therapeutic Potential of Regorafenib\u2014A Multikinase Inhibitor in Pulmonary Hypertension. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031502"},{"key":"ref_95","first-page":"399","article-title":"Regulation of PTEN by Rho small GTPases","volume":"7","author":"Li","year":"2005","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1159\/000078406","article-title":"Rho-ROCK Signal Pathway Regulates Microtubule-Based Process Formation of Cultured Podocytes\u2014Inhibition of ROCK Promoted Process Elongation","volume":"97","author":"Gao","year":"2004","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6059","DOI":"10.1038\/sj.onc.1203987","article-title":"Rho-kinase\/ROCK is involved in cytokinesis through the phosphorylation of myosin light chain and not ezrin\/radixin\/moesin proteins at the cleavage furrow","volume":"19","author":"Kosako","year":"2000","journal-title":"Oncogene"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1083\/jcb.143.5.1249","article-title":"Roles of Rho-associated Kinase in Cytokinesis; Mutations in Rho-associated Kinase Phosphorylation Sites Impair Cytokinetic Segregation of Glial Filaments","volume":"143","author":"Yasui","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nrm1128","article-title":"ROCKs: Multifunctional kinases in cell behaviour","volume":"4","author":"Riento","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1164\/rccm.200805-691OC","article-title":"RhoA and Rho Kinase Activation in Human Pulmonary Hypertension","volume":"179","author":"Guilluy","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pupt.2017.08.002","article-title":"Effects of fasudil on pulmonary hypertension in clinical practice","volume":"46","author":"Zhang","year":"2017","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Otani, N., Tomoe, T., Kawabe, A., Sugiyama, T., Horie, Y., Sugimura, H., Yasu, T., and Nakamoto, T. (2022). Recent Advances in the Treatment of Pulmonary Arterial Hypertension. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101277"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"L656","DOI":"10.1152\/ajplung.00090.2003","article-title":"Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase","volume":"287","author":"Fagan","year":"2004","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1183\/09031936.00140309","article-title":"Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertension","volume":"36","author":"Dahal","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_105","first-page":"334","article-title":"Analysis of Pulmonary Vasodilator Responses to SB-772077-B [4-(7-((3-Amino-1-pyrrolidinyl)carbonyl)-1-ethyl-1H-imidazo(4,5-c)pyridin-2-yl)-1,2,5-oxadiazol-3-amine], a Novel Aminofurazan-Based Rho Kinase Inhibitor","volume":"330","author":"Dhaliwal","year":"2009","journal-title":"Experiment"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1136\/hrt.2003.029470","article-title":"Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension","volume":"91","author":"Fukumoto","year":"2005","journal-title":"Heart"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1253\/circj.70.174","article-title":"Beneficial Acute Effects of Rho-Kinase Inhibitor in Patients With Pulmonary Arterial Hypertension","volume":"70","author":"Ishikura","year":"2006","journal-title":"Circ. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s00380-009-1176-8","article-title":"Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension","volume":"25","author":"Fujita","year":"2010","journal-title":"Heart Vessel."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ijcard.2014.09.101","article-title":"Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: A randomized, controlled, crossover study","volume":"177","author":"Jiang","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1253\/circj.CJ-13-0443","article-title":"Double-Blind, Placebo-Controlled Clinical Trial With a Rho-Kinase Inhibitor in Pulmonary Arterial Hypertension","volume":"77","author":"Fukumoto","year":"2013","journal-title":"Circ. J."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Ranchoux, B., Meloche, J., Paulin, R., Boucherat, O., Provencher, S., and Bonnet, S. (2016). DNA Damage and Pulmonary Hypertension. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060990"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00109-012-0982-0","article-title":"FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: Therapeutic benefits of dichloroacetate","volume":"91","author":"Piao","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1161\/hc0202.101974","article-title":"Dichloroacetate, a Metabolic Modulator, Prevents and Reverses Chronic Hypoxic Pulmonary Hypertension in Rats","volume":"105","author":"Michelakis","year":"2002","journal-title":"Circulation"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1161\/CIRCRESAHA.120.316443","article-title":"Epigenetic Metabolic Reprogramming of Right Ventricular Fibroblasts in Pulmonary Arterial Hypertension","volume":"126","author":"Tian","year":"2020","journal-title":"Circ. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"eaao4583","DOI":"10.1126\/scitranslmed.aao4583","article-title":"Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients","volume":"9","author":"Michelakis","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1164\/rccm.201703-0502OC","article-title":"ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension","volume":"197","author":"Budas","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1164\/rccm.201708-1767ED","article-title":"Therapeutic Value of ASK1 Inhibition in Pulmonary Arterial Hypertension","volume":"197","author":"Boucherat","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S2213-2600(21)00032-1","article-title":"Selonsertib in adults with pulmonary arterial hypertension (ARROW): A randomised, double-blind, placebo-controlled, phase 2 trial","volume":"10","author":"Rosenkranz","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.ijcard.2016.08.330","article-title":"Ranolazine as a novel therapy for pulmonary arterial hypertension","volume":"223","author":"Gong","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/cvr\/cvu188","article-title":"Ranolazine prevents INaL enhancement and blunts myocardial remodelling in a model of pulmonary hypertension","volume":"104","author":"Rocchetti","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_121","first-page":"480","article-title":"Ranolazine Reduces Remodeling of the Right Ventricle and Provoked Arrhythmias in Rats with Pulmonary Hypertension","volume":"353","author":"Liles","year":"2015","journal-title":"Experiment"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/ejhf.50","article-title":"Ranolazine protects from doxorubicin-induced oxidative stress and cardiac dysfunction","volume":"16","author":"Tocchetti","year":"2014","journal-title":"Eur. J. Heart Fail."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1086\/683813","article-title":"Phase I Safety Study of Ranolazine in Pulmonary Arterial Hypertension","volume":"5","author":"Schilz","year":"2015","journal-title":"Pulm. Circ."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1086\/682427","article-title":"Effects of Ranolazine on Exercise Capacity, Right Ventricular Indices, and Hemodynamic Characteristics in Pulmonary Arterial Hypertension: A Pilot Study","volume":"5","author":"Khan","year":"2015","journal-title":"Pulm. Circ."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e000736","DOI":"10.1136\/openhrt-2017-000736","article-title":"Rationale and design of the ranolazine PH\u2013RV study: A multicentred randomised and placebo-controlled study of ranolazine to improve RV function in patients with non-group 2 pulmonary hypertension","volume":"5","author":"Han","year":"2018","journal-title":"Open Heart"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"44ra58","DOI":"10.1126\/scitranslmed.3001327","article-title":"Fatty Acid Oxidation and Malonyl-CoA Decarboxylase in the Vascular Remodeling of Pulmonary Hypertension","volume":"2","author":"Sutendra","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Leopold, J.A., and Maron, B.A. (2016). Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050761"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Sharma, S., and Aldred, M.A. (2020). DNA Damage and Repair in Pulmonary Arterial Hypertension. Genes, 11.","DOI":"10.3390\/genes11101224"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Xu, D., Hu, Y.-H., Gou, X., Li, F.-Y., Yang, X.-Y., Li, Y.-M., and Chen, F. (2022). Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension. Molecules, 27.","DOI":"10.3390\/molecules27123724"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1161\/HYPERTENSIONAHA.119.14013","article-title":"Endothelial-to-Mesenchymal Transition and Inflammation Play Key Roles in Cyclophilin A\u2013Induced Pulmonary Arterial Hypertension","volume":"76","author":"Xue","year":"2020","journal-title":"Hypertension"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1002\/ctm2.175","article-title":"Retracted: CD248 as a novel therapeutic target in pulmonary arterial hypertension","volume":"10","author":"Xu","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1089\/ars.2018.7699","article-title":"Redox Regulation of Ion Channels and Receptors in Pulmonary Hypertension","volume":"31","author":"Resta","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/FJC.0000000000000862","article-title":"Dihydroartemisinin Attenuates Pulmonary Hypertension Through Inhibition of Pulmonary Vascular Remodeling in Rats","volume":"76","author":"Tang","year":"2020","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.bbrc.2018.10.176","article-title":"Anti-hypoxic effect of dihydroartemisinin on pulmonary artery endothelial cells","volume":"506","author":"Yu","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1089\/dna.2021.1113","article-title":"Dihydroartemisinin Attenuates Hypoxic Pulmonary Hypertension via the Downregulation of miR-335 Targeting Vangl2","volume":"41","author":"Li","year":"2022","journal-title":"DNA Cell Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/0262-1746(82)90024-5","article-title":"Antithrombotic activity and the mechanism of action of trapidil (Rocornal\u00ae)","volume":"9","author":"Suzuki","year":"1982","journal-title":"Prostaglandins Leukot. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.biopha.2018.04.001","article-title":"Trapidil improves hemodynamic, echocardiographic and redox state parameters of right ventricle in monocrotaline-induced pulmonary arterial hypertension model","volume":"103","author":"Lacerda","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/cvr\/cvq370","article-title":"Nitrite in pulmonary arterial hypertension: Therapeutic avenues in the setting of dysregulated arginine\/nitric oxide synthase signalling","volume":"89","author":"Zuckerbraun","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_139","first-page":"e89620","article-title":"Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction","volume":"1","author":"Simon","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.redox.2014.06.010","article-title":"Coenzyme Q supplementation in pulmonary arterial hypertension","volume":"2","author":"Sharp","year":"2014","journal-title":"Redox Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1152\/jappl.2001.90.4.1299","article-title":"Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia","volume":"90","author":"Hoshikawa","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1378\/chest.117.1.19","article-title":"Hyperuricemia in Severe Pulmonary Hypertension","volume":"117","author":"Voelkel","year":"2000","journal-title":"Chest"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1053\/rmed.2003.1440","article-title":"Hyperuricemia as a prognostic factor in pulmonary arterial hypertension","volume":"97","author":"Bendayan","year":"2003","journal-title":"Respir. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1183\/09031936.00013309","article-title":"Increased xanthine oxidase activity in idiopathic pulmonary arterial hypertension","volume":"34","author":"Spiekermann","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1086\/677370","article-title":"Vascular Stiffening in Pulmonary Hypertension: Cause or Consequence? (2013 Grover Conference Series)","volume":"4","author":"Tan","year":"2014","journal-title":"Pulm. Circ."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"H1322","DOI":"10.1152\/ajpheart.00136.2018","article-title":"Role of extracellular matrix in the pathogenesis of pulmonary arterial hypertension","volume":"315","author":"Thenappan","year":"2018","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1161\/01.RES.66.4.968","article-title":"Collagen and elastin metabolism in hypertensive pulmonary arteries of rats","volume":"66","author":"Poiani","year":"1990","journal-title":"Circ. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1161\/01.RES.79.6.1131","article-title":"Tenascin-C Is Induced With Progressive Pulmonary Vascular Disease in Rats and Is Functionally Related to Increased Smooth Muscle Cell Proliferation","volume":"79","author":"Jones","year":"1996","journal-title":"Circ. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.ajpath.2011.05.051","article-title":"Neutrophil Elastase Is Produced by Pulmonary Artery Smooth Muscle Cells and Is Linked to Neointimal Lesions","volume":"179","author":"Kim","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/(SICI)1097-4652(199603)166:3<495::AID-JCP4>3.0.CO;2-K","article-title":"Exogenous leukocyte and endogenous elastases can mediate mitogenic activity in pulmonary artery smooth muscle cells by release of extracellular matrix-bound basic fibroblast growth factor","volume":"166","author":"Thompson","year":"1996","journal-title":"J. Cell. Physiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.celrep.2015.09.049","article-title":"Matrix Remodeling Promotes Pulmonary Hypertension through Feedback Mechanoactivation of the YAP\/TAZ-miR-130\/301 Circuit","volume":"13","author":"Bertero","year":"2015","journal-title":"Cell Rep."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1089\/104303403765701150","article-title":"Inhibition of Matrix Metalloproteinases by Lung TIMP-1 Gene Transfer Limits Monocrotaline-Induced Pulmonary Vascular Remodeling in Rats","volume":"14","author":"Frisdal","year":"2003","journal-title":"Hum. Gene Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/j.1440-1681.2007.04618.x","article-title":"Amlodipine prevents monocrotaline-induced pulmonary arterial hypertension and prolongs survival in rats independent of blood pressure lowering","volume":"34","author":"Mawatari","year":"2007","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4070\/kcj.2011.41.2.83","article-title":"Gene Expressions of Nitric Oxide Synthase and Matrix Metalloproteinase-2 in Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment","volume":"41","author":"Koo","year":"2011","journal-title":"Korean Circ. J."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1023\/B:HREV.0000011395.11179.af","article-title":"Matrix Metalloproteinase Inhibitor Development and the Remodeling of Drug Discovery","volume":"9","author":"Peterson","year":"2004","journal-title":"Heart Fail. Rev."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/76282","article-title":"Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor","volume":"6","author":"Cowan","year":"2000","journal-title":"Nat. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1172\/JCI6539","article-title":"Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease","volume":"105","author":"Cowan","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1161\/01.RES.64.4.814","article-title":"SC-39026, a serine elastase inhibitor, prevents muscularization of peripheral arteries, suggesting a mechanism of monocrotaline-induced pulmonary hypertension in rats","volume":"64","author":"Ilkiw","year":"1989","journal-title":"Circ. Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/0006-2952(89)90084-1","article-title":"Monocrotaline-induced cardiopulmonary injury in rats","volume":"38","author":"Molteni","year":"1989","journal-title":"Biochem. Pharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1161\/hc0402.102866","article-title":"Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension","volume":"105","author":"Zaidi","year":"2002","journal-title":"Circulation"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1164\/rccm.201412-2291OC","article-title":"Elafin Reverses Pulmonary Hypertension via Caveolin-1\u2013Dependent Bone Morphogenetic Protein Signaling","volume":"191","author":"Nickel","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.chest.2021.06.028","article-title":"Severe Pulmonary Arterial Hypertension Is Characterized by Increased Neutrophil Elastase and Relative Elafin Deficiency","volume":"160","author":"Sweatt","year":"2021","journal-title":"Chest"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1183\/09031936.00030312","article-title":"A potential role for insulin resistance in experimental pulmonary hypertension","volume":"41","author":"West","year":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1183\/09031936.00000508","article-title":"Insulin resistance in pulmonary arterial hypertension","volume":"33","author":"Zamanian","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"496","DOI":"10.2337\/diabetes.55.02.06.db05-1064","article-title":"Activation of the AMP-Activated Kinase by Antidiabetes Drug Metformin Stimulates Nitric Oxide Synthesis In Vivo by Promoting the Association of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase","volume":"55","author":"Davis","year":"2006","journal-title":"Diabetes"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1086\/688034","article-title":"Novel Signaling Pathways in Pulmonary Arterial Hypertension (2015 Grover Conference Series)","volume":"6","author":"Awad","year":"2016","journal-title":"Pulm. Circ."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/j.1476-5381.2009.00445.x","article-title":"Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertension","volume":"158","author":"Agard","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e018349","DOI":"10.1161\/JAHA.120.018349","article-title":"Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension","volume":"9","author":"Brittain","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/2231-4040.90879","article-title":"The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases","volume":"2","author":"Tyagi","year":"2011","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/1753465809369619","article-title":"PPAR\u03b3 as a potential therapeutic target in pulmonary hypertension","volume":"4","author":"Sutliff","year":"2010","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"eaao0303","DOI":"10.1126\/scitranslmed.aao0303","article-title":"PPAR\u03b3 agonist pioglitazone reverses pulmonary hypertension and prevents right heart failure via fatty acid oxidation","volume":"10","author":"Legchenko","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"H185","DOI":"10.1152\/ajpheart.00081.2008","article-title":"The transcriptional coactivator PGC-1\u03b1 is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis","volume":"295","author":"Lehman","year":"2008","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.lfs.2013.12.208","article-title":"Activation of PPAR-\u03b3 ameliorates pulmonary arterial hypertension via inducing heme oxygenase-1 and p21WAF1: An in vivo study in rats","volume":"98","author":"Zhang","year":"2014","journal-title":"Life Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3892\/br.2015.465","article-title":"Activation of peroxisome proliferator-activated receptor \u03b3 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats","volume":"3","author":"Xie","year":"2015","journal-title":"Biomed. Rep."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2004633","DOI":"10.1183\/13993003.04633-2020","article-title":"Neurohormonal modulation in pulmonary arterial hypertension","volume":"58","author":"Peters","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1111\/bph.14968","article-title":"Metabolic syndrome, neurohumoral modulation, and pulmonary arterial hypertension","volume":"177","author":"Maron","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1172\/JCI115659","article-title":"Beta-adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms","volume":"89","author":"Bristow","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"e002636","DOI":"10.1161\/CIRCHEARTFAILURE.115.002636","article-title":"Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension","volume":"9","author":"Rain","year":"2016","journal-title":"Circ. Heart Fail."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1161\/CIRCULATIONAHA.114.006980","article-title":"Emerging Concepts in the Molecular Basis of Pulmonary Arterial Hypertension","volume":"131","author":"Maron","year":"2015","journal-title":"Circulation"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Lunar, I., Pereda, D., Ibanez, B., and Garc\u00eda-\u00c1lvarez, A. (2020). Neurohormonal Modulation as a Therapeutic Target in Pulmonary Hypertension. Cells, 9.","DOI":"10.3390\/cells9112521"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1702638","DOI":"10.1183\/13993003.02638-2017","article-title":"A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension","volume":"51","author":"Hemnes","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1902416","DOI":"10.1183\/13993003.02416-2019","article-title":"Angiotensin converting enzyme 2 and angiotensin (1\u20137) axis in pulmonary arterial hypertension","volume":"56","author":"Sandoval","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e003703","DOI":"10.1161\/CIRCHEARTFAILURE.116.003703","article-title":"Use of \u03b2-Blockers in Pulmonary Hypertension","volume":"10","author":"Perros","year":"2017","journal-title":"Circ. Heart Fail."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"106974","DOI":"10.1016\/j.vph.2022.106974","article-title":"Beta-blockers in pulmonary arterial hypertension: Time for a second thought?","volume":"144","author":"Badagliacca","year":"2022","journal-title":"Vasc. Pharmacol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1183\/09031936.00215514","article-title":"Outcomes of \u03b2-blocker use in pulmonary arterial hypertension: A propensity-matched analysis","volume":"46","author":"Bandyopadhyay","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1164\/rccm.201311-2025LE","article-title":"Treatment of Group I Pulmonary Arterial Hypertension with Carvedilol Is Safe","volume":"189","author":"Grinnan","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1161\/CIRCHEARTFAILURE.111.964494","article-title":"Bisoprolol Delays Progression Towards Right Heart Failure in Experimental Pulmonary Hypertension","volume":"5","author":"Handoko","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1183\/13993003.00090-2016","article-title":"Bisoprolol in idiopathic pulmonary arterial hypertension: An explorative study","volume":"48","author":"Allaart","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/pul2.12024","article-title":"An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension","volume":"12","author":"Simon","year":"2022","journal-title":"Pulm. Circ."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1086\/675984","article-title":"The Role of the Renin-Angiotensin-Aldosterone System in the Pathobiology of Pulmonary Arterial Hypertension (2013 Grover Conference Series)","volume":"4","author":"Maron","year":"2014","journal-title":"Pulm. Circ."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Beckmann, T., Shelley, P., Patel, D., Vorla, M., and Kalra, D.K. (2022). Strategizing Drug Therapies in Pulmonary Hypertension for Improved Outcomes. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101242"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"20458940211045618","DOI":"10.1177\/20458940211045618","article-title":"Effect of spironolactone use in pulmonary arterial hypertension\u2014Analysis from pivotal trial databases","volume":"11","author":"Safdar","year":"2021","journal-title":"Pulm. Circ."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"H2035","DOI":"10.1152\/ajpheart.00552.2010","article-title":"Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression","volume":"300","author":"Favre","year":"2011","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"L678","DOI":"10.1152\/ajplung.00300.2012","article-title":"Mineralocorticoid receptor antagonism attenuates experimental pulmonary hypertension","volume":"304","author":"Preston","year":"2013","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/j.1475-097X.1993.tb00482.x","article-title":"Effect of vasoactive intestinal polypeptide (VIP) on pulmonary ventilation-perfusion relationships and central haemodynamics in healthy subjects","volume":"13","author":"Soderman","year":"1993","journal-title":"Clin. Physiol. Funct. Imaging"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0196-9781(99)00202-8","article-title":"Immunohistochemical localization and distribution of VIP\/PACAP receptors in human lung\u2606","volume":"21","author":"Busto","year":"2000","journal-title":"Peptides"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1172\/JCI17500","article-title":"Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension","volume":"111","author":"Petkov","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1183\/09031936.00050008","article-title":"Inhalation of vasoactive intestinal peptide in pulmonary hypertension","volume":"32","author":"Leuchte","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"e12088","DOI":"10.1002\/pul2.12088","article-title":"A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2)","volume":"12","author":"Lazarus","year":"2022","journal-title":"Pulm. Circ."},{"key":"ref_200","first-page":"PA1919","article-title":"ELEVATE 2: A multicenter study of rodatristat ethyl in patients with WHO Group 1 pulmonary arterial hypertension (PAH)","volume":"58","author":"Lazarus","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1097\/SHK.0b013e31816f239f","article-title":"Exogenous estrogen rapidly attenuates pulmonary artery vasoreactivity and acute hypoxic pulmonary vasoconstriction","volume":"30","author":"Lahm","year":"2008","journal-title":"Shock"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"e13157","DOI":"10.14814\/phy2.13157","article-title":"Estrogen maintains mitochondrial content and function in the right ventricle of rats with pulmonary hypertension","volume":"5","author":"Liu","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1164\/rccm.201509-1785OC","article-title":"Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated with Pulmonary Arterial Hypertension in Men","volume":"193","author":"Ventetuolo","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"110355","DOI":"10.1016\/j.biopha.2020.110355","article-title":"Investigational pharmacotherapy and immunotherapy of pulmonary arterial hypertension: An update","volume":"129","author":"Yang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1164\/rccm.201605-1024OC","article-title":"Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial","volume":"195","author":"Kawut","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1602337","DOI":"10.1183\/13993003.02337-2016","article-title":"Oestrogen inhibition reverses pulmonary arterial hypertension and associated metabolic defects","volume":"50","author":"Chen","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ando.2011.12.005","article-title":"Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): A pilot study","volume":"73","author":"Savineau","year":"2012","journal-title":"Ann. D\u2019Endocrinol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jacc.2011.02.057","article-title":"Iron Deficiency and Raised Hepcidin in Idiopathic Pulmonary Arterial Hypertension","volume":"58","author":"Rhodes","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"5999","DOI":"10.1113\/jphysiol.2008.160960","article-title":"The increase in pulmonary arterial pressure caused by hypoxia depends on iron status","volume":"586","author":"Smith","year":"2008","journal-title":"J. Physiol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1152\/jappl.2000.89.2.680","article-title":"Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans","volume":"89","author":"Ren","year":"2000","journal-title":"J. Appl. Physiol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1161\/CIRCRESAHA.116.305265","article-title":"Iron Homeostasis and Pulmonary Hypertension","volume":"116","author":"Cotroneo","year":"2015","journal-title":"Circ. Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"104664","DOI":"10.1016\/j.phrs.2020.104664","article-title":"The role of hepcidin and iron homeostasis in atherosclerosis","volume":"153","author":"Wunderer","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"641","DOI":"10.3389\/fphys.2018.00641","article-title":"Pulmonary Arterial Hypertension: Iron Matters","volume":"9","author":"Ramakrishnan","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"5669412","DOI":"10.1155\/2021\/5669412","article-title":"Iron Metabolism and Idiopathic Pulmonary Arterial Hypertension: New Insights from Bioinformatic Analysis","volume":"2021","author":"Zou","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1513\/AnnalsATS.202009-1131OC","article-title":"Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials","volume":"18","author":"Howard","year":"2021","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1164\/ajrccm.158.6.9805002","article-title":"Monoclonal Endothelial Cells in Appetite Suppressant\u2013associated Pulmonary Hypertension","volume":"158","author":"Tuder","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1161\/CIRCULATIONAHA.113.006167","article-title":"Role for DNA Damage Signaling in Pulmonary Arterial Hypertension","volume":"129","author":"Meloche","year":"2014","journal-title":"Circulation"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"H1798","DOI":"10.1152\/ajpheart.00654.2011","article-title":"Dehydroepiandrosterone inhibits the Src\/STAT3 constitutive activation in pulmonary arterial hypertension","volume":"301","author":"Paulin","year":"2011","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1164\/rccm.201411-2128OC","article-title":"Increased Mutagen Sensitivity and DNA Damage in Pulmonary Arterial Hypertension","volume":"192","author":"Federici","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1164\/rccm.202009-3706ED","article-title":"In Defense of the Nucleus: NUDT1 and Oxidative DNA Damage in Pulmonary Arterial Hypertension","volume":"203","author":"Agarwal","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00210-019-01615-4","article-title":"Paclitaxel alleviates monocrotaline-induced pulmonary arterial hypertension via inhibition of FoxO1-mediated autophagy","volume":"392","author":"Feng","year":"2019","journal-title":"Naunyn-Schmiedebergs Arch. Pharmacol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/ncb2069","article-title":"Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity","volume":"12","author":"Zhao","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"11023","DOI":"10.1038\/ncomms11023","article-title":"FoxO1-mediated autophagy is required for NK cell development and innate immunity","volume":"7","author":"Wang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1378\/chest.94.6.1249","article-title":"Balloon Angioplasty in the Treatment of Pulmonary Hypertension Caused by Pulmonary Embolism","volume":"94","author":"Voorburg","year":"1988","journal-title":"Chest"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1161\/01.CIR.103.1.10","article-title":"Balloon Pulmonary Angioplasty for Treatment of Chronic Thromboembolic Pulmonary Hypertension","volume":"103","author":"Feinstein","year":"2001","journal-title":"Circulation"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.12998\/wjcc.v8.i13.2679","article-title":"Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: State of the art","volume":"8","author":"Jin","year":"2020","journal-title":"World J. Clin. Cases"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"518","DOI":"10.4244\/EIJV10I4A89","article-title":"Balloon pulmonary angioplasty: An additional treatment option to improve the prognosis of patients with chronic thromboembolic pulmonary hypertension","volume":"10","author":"Taniguchi","year":"2014","journal-title":"Eurointervention"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1802095","DOI":"10.1183\/13993003.02095-2018","article-title":"French experience of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension","volume":"53","author":"Brenot","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"e004029","DOI":"10.1161\/CIRCOUTCOMES.117.004029","article-title":"Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension","volume":"10","author":"Ogawa","year":"2017","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"ehz745-1061","DOI":"10.1093\/eurheartj\/ehz745.1061","article-title":"P4679Changes in systemic inflammation and endothelial dysfunction after balloon pulmonary angioplasty","volume":"40","author":"Magon","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1161\/CIRCULATIONAHA.115.019470","article-title":"Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy","volume":"133","author":"Cannon","year":"2016","journal-title":"Circulation"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"e003318","DOI":"10.1161\/CIRCINTERVENTIONS.115.003318","article-title":"Novel Angiographic Classification of Each Vascular Lesion in Chronic Thromboembolic Pulmonary Hypertension Based on Selective Angiogram and Results of Balloon Pulmonary Angioplasty","volume":"9","author":"Kawakami","year":"2016","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1001518","DOI":"10.3389\/fcvm.2022.1001518","article-title":"Balloon pulmonary angioplasty can be an effective and safe therapeutic option in non-surgical elderly patients","volume":"9","author":"Cebada","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1164\/rccm.200912-1856OC","article-title":"Prognostic Significance of Sympathetic Nervous System Activation in Pulmonary Arterial Hypertension","volume":"181","author":"Ciarka","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1183\/09031936.00145708","article-title":"Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension","volume":"34","author":"Wensel","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1161\/01.CIR.0000140724.90898.D3","article-title":"Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension","volume":"110","author":"Ciarka","year":"2004","journal-title":"Circulation"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.jacc.2014.11.050","article-title":"Nebivolol for Improving Endothelial Dysfunction, Pulmonary Vascular Remodeling, and Right Heart Function in Pulmonary Hypertension","volume":"65","author":"Perros","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1016\/j.jcin.2015.09.015","article-title":"Pulmonary Artery Denervation Attenuates Pulmonary Arterial Remodeling in Dogs With Pulmonary Arterial Hypertension Induced by Dehydrogenized Monocrotaline","volume":"8","author":"Zhou","year":"2015","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4244\/EIJV9I2A43","article-title":"Percutaneous pulmonary artery denervation completely abolishes experimental pulmonary arterial hypertension in vivo","volume":"9","author":"Chen","year":"2013","journal-title":"Eurointervention"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"e002569","DOI":"10.1161\/CIRCINTERVENTIONS.115.002569","article-title":"Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension","volume":"8","author":"Rothman","year":"2015","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.jacc.2013.05.075","article-title":"Pulmonary Artery Denervation to Treat Pulmonary Arterial Hypertension","volume":"62","author":"Chen","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jcin.2018.09.021","article-title":"Pulmonary Artery Denervation Significantly Increases 6-Min Walk Distance for Patients with Combined Pre- and Post-Capillary Pulmonary Hypertension Associated with Left Heart Failure","volume":"12","author":"Zhang","year":"2019","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1016\/j.jcin.2015.10.022","article-title":"Pulmonary Artery Denervation for Pulmonary Artery Hypertension","volume":"8","author":"Rubin","year":"2015","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1016\/j.jcin.2022.09.013","article-title":"Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized Trial","volume":"15","author":"Zhang","year":"2022","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1378\/chest.06-1227","article-title":"Atrial Septostomy in Treatment of End-Stage Right Heart Failure in Patients with Pulmonary Hypertension","volume":"131","author":"Kurzyna","year":"2007","journal-title":"Chest"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/0002-9149(83)90678-1","article-title":"Atrial septostomy as palliative therapy for refractory primary pulmonary hypertension","volume":"51","author":"Rich","year":"1983","journal-title":"Am. J. Cardiol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1183\/09031936.00072210","article-title":"Effect of atrial septostomy on the survival of patients with severe pulmonary arterial hypertension","volume":"38","author":"Sandoval","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1136\/heartjnl-2022-321212","article-title":"First in-human modified atrial septostomy combining radiofrequency ablation and balloon dilation","volume":"108","author":"Yan","year":"2022","journal-title":"Heart"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1016\/j.jacc.2019.02.067","article-title":"Immunotherapy of Endothelin-1 Receptor Type A for Pulmonary Arterial Hypertension","volume":"73","author":"Dai","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.healun.2012.03.010","article-title":"Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression","volume":"31","author":"Bockmeyer","year":"2012","journal-title":"J. Heart Lung Transplant."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"L1182","DOI":"10.1152\/ajplung.00020.2006","article-title":"Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension","volume":"292","author":"Reynolds","year":"2007","journal-title":"Am. J. Physiol. Cell. Mol. 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