{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:47:11Z","timestamp":1792813631921,"version":"4.5.0"},"reference-count":100,"publisher":"Elsevier BV","issue":"25","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,12,24]],"date-time":"2014-12-24T00:00:00Z","timestamp":1419379200000},"content-version":"vor","delay-in-days":388,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of the American College of Cardiology"],"published-print":{"date-parts":[[2013,12]]},"DOI":"10.1016\/j.jacc.2013.10.025","type":"journal-article","created":{"date-parts":[[2013,12,16]],"date-time":"2013-12-16T21:21:25Z","timestamp":1387228885000},"page":"D4-D12","source":"Crossref","is-referenced-by-count":527,"special_numbering":"S","title":["Relevant Issues in the Pathology and Pathobiology of Pulmonary Hypertension"],"prefix":"10.1016","volume":"62","author":[{"given":"Rubin M.","family":"Tuder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Archer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dorfm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serpil C.","family":"Erzurum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Guignabert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Michelakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Rabinovitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Schermuly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R.","family":"Stenmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas W.","family":"Morrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jacc.2013.10.025_bib1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jacc.2009.04.009","article-title":"Development and pathology of pulmonary hypertension","volume":"54","author":"Tuder","year":"2009","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2013.10.025_bib2","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1016\/j.jacc.2009.04.018","article-title":"Cellular and molecular basis of pulmonary arterial hypertension","volume":"54","author":"Morrell","year":"2009","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2013.10.025_bib3","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1165\/rcmb.F307","article-title":"One hundred years of research in the pathogenesis of pulmonary hypertension","volume":"33","author":"Zaiman","year":"2005","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jacc.2013.10.025_bib4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1161\/CIRCULATIONAHA.105.540542","article-title":"Epidermal growth factor receptor blockade mediates smooth muscle cell apoptosis and improves survival in rats with pulmonary hypertension","volume":"112","author":"Merklinger","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2013.10.025_bib5","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1172\/JCI35070","article-title":"Endothelial-derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents","volume":"119","author":"Izikki","year":"2009","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jacc.2013.10.025_bib6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1164\/rccm.200707-1037OC","article-title":"Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension","volume":"178","author":"Perros","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib7","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1172\/JCI24838","article-title":"Reversal of experimental pulmonary hypertension by PDGF inhibition","volume":"115","author":"Schermuly","year":"2005","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jacc.2013.10.025_bib8","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1161\/CIRCULATIONAHA.108.821504","article-title":"Altered bone morphogenetic protein and transforming growth factor-beta signaling in rat models of pulmonary hypertension: potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease","volume":"119","author":"Long","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2013.10.025_bib9","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1164\/rccm.200707-1083OC","article-title":"Role of TGF-\u03b2\/ALK5\u00a0kinase in monocrotaline-induced pulmonary hypertension","volume":"177","author":"Zaiman","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nm.3040","article-title":"An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension","volume":"19","author":"Kim","year":"2013","journal-title":"Nat Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib11","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.20101812","article-title":"Role for miR-204 in human pulmonary arterial hypertension","volume":"208","author":"Courboulin","year":"2011","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2174\/157016112799959413","article-title":"Genetically modified endothelial progenitor cells in the therapy of cardiovascular disease and pulmonary hypertension","volume":"10","author":"Lavoie","year":"2012","journal-title":"Curr Vasc Pharmacol"},{"key":"10.1016\/j.jacc.2013.10.025_bib13","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1182\/blood-2012-03-419275","article-title":"Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension","volume":"120","author":"Asosingh","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.jacc.2013.10.025_bib14","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1002\/art.34501","article-title":"Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension","volume":"64","author":"Gunther","year":"2012","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jacc.2013.10.025_bib15","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":"10.1016\/j.jacc.2013.10.025_bib16","doi-asserted-by":"crossref","first-page":"L725","DOI":"10.1152\/ajplung.00186.2013","article-title":"Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease","volume":"305","author":"Hunt","year":"2013","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jacc.2013.10.025_bib17","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/CIRCULATIONAHA.108.847707","article-title":"Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies","volume":"121","author":"Archer","year":"2010","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2013.10.025_bib18","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1161\/01.RES.0000261658.12024.18","article-title":"Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats","volume":"100","author":"Oka","year":"2007","journal-title":"Circ Res"},{"key":"10.1016\/j.jacc.2013.10.025_bib19","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1086\/303059","article-title":"Familial primary pulmonary hypertension (gene PPH1) Is caused by mutations in the bone morphogenetic protein receptor-II gene","volume":"67","author":"Deng","year":"2000","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.jacc.2013.10.025_bib20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/79226","article-title":"Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension","volume":"26","author":"Lane","year":"2000","journal-title":"Nat Genet"},{"key":"10.1016\/j.jacc.2013.10.025_bib21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/humu.20285","article-title":"Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension","volume":"27","author":"Machado","year":"2006","journal-title":"Hum Mutat"},{"key":"10.1016\/j.jacc.2013.10.025_bib22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1056\/NEJM200108023450503","article-title":"Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia","volume":"345","author":"Trembath","year":"2001","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib23","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1136\/thx.2003.11890","article-title":"Endoglin germline mutation in a patient with hereditary haemorrhagic telangiectasia and dexfenfluramine\u00a0associated pulmonary arterial hypertension","volume":"59","author":"Chaouat","year":"2004","journal-title":"Thorax"},{"key":"10.1016\/j.jacc.2013.10.025_bib24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1136\/jmg.2008.062703","article-title":"A\u00a0new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension","volume":"46","author":"Shintani","year":"2009","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.jacc.2013.10.025_bib25","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1161\/CIRCGENETICS.111.961888","article-title":"Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension","volume":"5","author":"Austin","year":"2012","journal-title":"Circ Cardiovasc Genet"},{"key":"10.1016\/j.jacc.2013.10.025_bib26","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa1211097","article-title":"A\u00a0novel channelopathy in pulmonary arterial hypertension","volume":"369","author":"Ma","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib27","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1164\/rccm.200908-1284OC","article-title":"Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation","volume":"181","author":"Girerd","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib28","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":"10.1016\/j.jacc.2013.10.025_bib29","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1161\/01.RES.88.1.e2","article-title":"Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension","volume":"88","author":"Yeager","year":"2001","journal-title":"Circ Res"},{"key":"10.1016\/j.jacc.2013.10.025_bib30","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1164\/rccm.201003-0491OC","article-title":"Somatic chromosome abnormalities in the lungs of patients with pulmonary arterial hypertension","volume":"182","author":"Aldred","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib31","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1073\/pnas.0605080104","article-title":"Alterations of cellular bioenergetics in pulmonary artery endothelial cells","volume":"104","author":"Xu","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jacc.2013.10.025_bib32","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":"10.1016\/j.jacc.2013.10.025_bib33","doi-asserted-by":"crossref","first-page":"L981","DOI":"10.1152\/ajplung.2000.278.5.L981","article-title":"Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia","volume":"278","author":"Aguirre","year":"2000","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jacc.2013.10.025_bib34","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/cvr\/8.6.745","article-title":"The genetic factor influencing pulmonary hypertension in cattle at high altitude","volume":"8","author":"Weir","year":"1974","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.jacc.2013.10.025_bib35","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3181\/00379727-164-40837","article-title":"Embryo transplanted calves: the pulmonary hypertensive trait is genetically transmitted","volume":"164","author":"Cruz","year":"1980","journal-title":"Proc Soc Exp Biol Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib36","doi-asserted-by":"crossref","first-page":"462","DOI":"10.4103\/2045-8932.93545","article-title":"High-altitude pulmonary hypertension in cattle (brisket disease): candidate genes and gene expression profiling of peripheral blood mononuclear cells","volume":"1","author":"Newman","year":"2011","journal-title":"Pulm Circ"},{"key":"10.1016\/j.jacc.2013.10.025_bib37","doi-asserted-by":"crossref","first-page":"L1013","DOI":"10.1152\/ajplung.00217.2009","article-title":"Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure","volume":"297","author":"Stenmark","year":"2009","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jacc.2013.10.025_bib38","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":"10.1016\/j.jacc.2013.10.025_bib39","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1165\/rcmb.2011-0296OC","article-title":"Copper-dependence of angioproliferation in pulmonary arterial hypertension in rats and humans","volume":"46","author":"Bogaard","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jacc.2013.10.025_bib40","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1161\/CIRCULATIONAHA.109.927681","article-title":"Formation of plexiform lesions in experimental severe pulmonary arterial hypertension","volume":"121","author":"Abe","year":"2010","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2013.10.025_bib41","doi-asserted-by":"crossref","first-page":"225S","DOI":"10.1378\/chest.114.3_Supplement.225S","article-title":"Primary pulmonary hypertension between inflammation and cancer","volume":"114","author":"Voelkel","year":"1999","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2013.10.025_bib42","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\u00a0Clin Invest"},{"key":"10.1016\/j.jacc.2013.10.025_bib43","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.2353\/ajpath.2010.090832","article-title":"Hypoxia inducible-factor1alpha regulates the metabolic shift of pulmonary hypertensive endothelial cells","volume":"176","author":"Fijalkowska","year":"2010","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jacc.2013.10.025_bib44","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1172\/JCI23203","article-title":"Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension","volume":"115","author":"McMurtry","year":"2005","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jacc.2013.10.025_bib45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"10.1016\/j.jacc.2013.10.025_bib46","doi-asserted-by":"crossref","first-page":"H570","DOI":"10.1152\/ajpheart.01324.2007","article-title":"Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1a}-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer","volume":"294","author":"Archer","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.jacc.2013.10.025_bib47","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1164\/rccm.201108-1536PP","article-title":"Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension","volume":"185","author":"Tuder","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib48","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.jacc.2013.10.025_bib49","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.jacc.2013.10.025_bib50","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-cellbio-092910-154237","article-title":"Aerobic glycolysis: meeting the metabolic requirements of cell proliferation","volume":"27","author":"Lunt","year":"2011","journal-title":"Annu Rev Cell Dev Biol"},{"key":"10.1016\/j.jacc.2013.10.025_bib51","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1164\/rccm.201009-1393PP","article-title":"HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease","volume":"183","author":"Shimoda","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib52","doi-asserted-by":"crossref","first-page":"25130","DOI":"10.1074\/jbc.M001914200","article-title":"Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing","volume":"275","author":"Chandel","year":"2000","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jacc.2013.10.025_bib53","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2353\/ajpath.2008.070705","article-title":"Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension","volume":"172","author":"Asosingh","year":"2008","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jacc.2013.10.025_bib54","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1164\/rccm.200810-1662OC","article-title":"Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension","volume":"180","author":"Toshner","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib55","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1182\/blood-2010-09-306357","article-title":"Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities","volume":"117","author":"Farha","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.jacc.2013.10.025_bib56","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":"10.1016\/j.jacc.2013.10.025_bib57","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1161\/CIRCRESAHA.111.263848","article-title":"Dynamin-related protein 1-mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension","volume":"110","author":"Marsboom","year":"2012","journal-title":"Circ Res"},{"key":"10.1016\/j.jacc.2013.10.025_bib58","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1164\/rccm.201209-1687OC","article-title":"PGC1alpha-mediated mitofusin-2 deficiency in female rats and humans with pulmonary arterial hypertension","volume":"187","author":"Ryan","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib59","doi-asserted-by":"crossref","first-page":"H77","DOI":"10.1152\/ajpheart.01386.2006","article-title":"Pulmonary arterial hypertension: a disease of tethers, SNAREs and SNAPs?","volume":"293","author":"Sehgal","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.jacc.2013.10.025_bib60","doi-asserted-by":"crossref","first-page":"229","DOI":"10.4103\/2045-8932.97613","article-title":"Activation of the unfolded protein response is associated with pulmonary hypertension","volume":"2","author":"Yeager","year":"2012","journal-title":"Pulm Circ"},{"key":"10.1016\/j.jacc.2013.10.025_bib61","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1161\/CIRCULATIONAHA.112.133413","article-title":"Attenuating endoplasmic reticulum stress as a novel therapeutic strategy in pulmonary hypertension","volume":"127","author":"Dromparis","year":"2013","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2013.10.025_bib62","doi-asserted-by":"crossref","first-page":"88ra55","DOI":"10.1126\/scitranslmed.3002194","article-title":"The role of nogo and the mitochondria-endoplasmic reticulum unit in pulmonary hypertension","volume":"3","author":"Sutendra","year":"2011","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1513\/AnnalsATS.201206-029OC","article-title":"Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year","volume":"10","author":"Lundgrin","year":"2013","journal-title":"Ann Am Thorac Soc"},{"key":"10.1016\/j.jacc.2013.10.025_bib64","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1164\/rccm.201108-1562OC","article-title":"Lung (1)(8)F-fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of pulmonary arterial hypertension","volume":"185","author":"Marsboom","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib65","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00109-013-1059-4","article-title":"A\u00a0metabolic remodeling in right ventricular hypertrophy is associated with decreased angiogenesis and a transition from a compensated to a decompensated state in pulmonary hypertension","volume":"91","author":"Sutendra","year":"2013","journal-title":"J\u00a0Mol Med (Berl)"},{"key":"10.1016\/j.jacc.2013.10.025_bib66","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1161\/01.RES.0000145360.16770.9f","article-title":"Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis","volume":"95","author":"McMurtry","year":"2004","journal-title":"Circ Res"},{"key":"10.1016\/j.jacc.2013.10.025_bib67","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0022-2143(98)90020-8","article-title":"Pulmonary hypertension and inflammation","volume":"132","author":"Tuder","year":"1998","journal-title":"J\u00a0Lab Clin Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib68","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/nature01320","article-title":"Points of control in inflammation","volume":"420","author":"Nathan","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.jacc.2013.10.025_bib69","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1164\/ajrccm.151.5.7735624","article-title":"Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension","volume":"151","author":"Humbert","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib70","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":"10.1016\/j.jacc.2013.10.025_bib71","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1183\/09031936.03.00038903","article-title":"Inflammation in pulmonary arterial hypertension","volume":"22","author":"Dorfmuller","year":"2003","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2013.10.025_bib72","first-page":"275","article-title":"Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension","volume":"144","author":"Tuder","year":"1994","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jacc.2013.10.025_bib73","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1164\/rccm.201202-0335OC","article-title":"Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension","volume":"186","author":"Savai","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib74","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1183\/09031936.00159911","article-title":"Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension","volume":"40","author":"Huertas","year":"2012","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2013.10.025_bib75","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000111548","article-title":"Increased regulatory and decreased CD8+ cytotoxic T cells in the blood of patients with idiopathic pulmonary arterial hypertension","volume":"75","author":"Ulrich","year":"2008","journal-title":"Respiration"},{"key":"10.1016\/j.jacc.2013.10.025_bib76","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1161\/CIRCULATIONAHA.112.110619","article-title":"Impaired natural killer cell phenotype and function in idiopathic and heritable pulmonary arterial hypertension","volume":"126","author":"Ormiston","year":"2012","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2013.10.025_bib77","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\u00a0Clin Invest"},{"key":"10.1016\/j.jacc.2013.10.025_bib78","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1182\/blood-2006-04-018796","article-title":"Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis","volume":"108","author":"Walmsley","year":"2006","journal-title":"Blood"},{"key":"10.1016\/j.jacc.2013.10.025_bib79","doi-asserted-by":"crossref","first-page":"e28578","DOI":"10.1371\/journal.pone.0028578","article-title":"Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice","volume":"6","author":"Bauer","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1016\/j.jacc.2013.10.025_bib80","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1164\/rccm.201105-0927OC","article-title":"Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension","volume":"185","author":"Perros","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib81","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1183\/09031936.00181410","article-title":"Targets of anti-endothelial cell antibodies in pulmonary hypertension and scleroderma","volume":"39","author":"Dib","year":"2012","journal-title":"Eur Resp J"},{"key":"10.1016\/j.jacc.2013.10.025_bib82","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1136\/thx.2004.029082","article-title":"Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension","volume":"60","author":"Tamby","year":"2005","journal-title":"Thorax"},{"key":"10.1016\/j.jacc.2013.10.025_bib83","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":"10.1016\/j.jacc.2013.10.025_bib84","doi-asserted-by":"crossref","first-page":"20S","DOI":"10.1378\/chest.10-0048","article-title":"Schistosomiasis-associated pulmonary hypertension: pulmonary vascular disease: the global perspective","volume":"137","author":"Graham","year":"2010","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2013.10.025_bib85","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1089\/aid.2011.0021","article-title":"Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension","volume":"28","author":"Almodovar","year":"2012","journal-title":"AIDS Res Hum Retroviruses"},{"key":"10.1016\/j.jacc.2013.10.025_bib86","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2353\/ajpath.2006.050599","article-title":"Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte\/macrophage lineage","volume":"168","author":"Frid","year":"2006","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jacc.2013.10.025_bib87","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.4049\/jimmunol.1100479","article-title":"Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe hypoxic pulmonary hypertension","volume":"187","author":"Li","year":"2011","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.jacc.2013.10.025_bib88","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ccm.2006.11.010","article-title":"Pathology of pulmonary hypertension","volume":"28","author":"Tuder","year":"2007","journal-title":"Clin Chest Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib89","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1152\/physiol.00053.2005","article-title":"Role of the adventitia in pulmonary vascular remodeling","volume":"21","author":"Stenmark","year":"2006","journal-title":"Physiology (Bethesda)"},{"key":"10.1016\/j.jacc.2013.10.025_bib90","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1161\/CIRCULATIONAHA.106.655837","article-title":"Diverse contribution of bone marrow-derived cells to vascular remodeling associated with pulmonary arterial hypertension and arterial neointimal formation","volume":"115","author":"Sahara","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2013.10.025_bib91","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1600-065X.1999.tb01318.x","article-title":"Integrating innate and adaptive immunity in the whole animal","volume":"169","author":"Lo","year":"1999","journal-title":"Immunol Rev"},{"key":"10.1016\/j.jacc.2013.10.025_bib92","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1471-4906(01)01863-4","article-title":"Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation","volume":"22","author":"Buckley","year":"2001","journal-title":"Trends Immunol"},{"key":"10.1016\/j.jacc.2013.10.025_bib93","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":"10.1016\/j.jacc.2013.10.025_bib94","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1189\/jlb.0409236","article-title":"The phenotype of murine wound macrophages","volume":"87","author":"Daley","year":"2010","journal-title":"J\u00a0Leukoc Biol"},{"key":"10.1016\/j.jacc.2013.10.025_bib95","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1182\/blood-2009-04-217620","article-title":"Epigenetic regulation of the alternatively activated macrophage phenotype","volume":"114","author":"Ishii","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.jacc.2013.10.025_bib96","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1172\/JCI45444","article-title":"Kruppel-like factor 4 regulates macrophage polarization","volume":"121","author":"Liao","year":"2011","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jacc.2013.10.025_bib97","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/ni.1920","article-title":"The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection","volume":"11","author":"Satoh","year":"2010","journal-title":"Nat Immunol"},{"key":"10.1016\/j.jacc.2013.10.025_bib98","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.jacc.2013.10.025_bib99","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nm.3145","article-title":"Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis","volume":"19","author":"Koeth","year":"2013","journal-title":"Nat Med"},{"key":"10.1016\/j.jacc.2013.10.025_bib100","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1161\/CIRCULATIONAHA.112.114173","article-title":"Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension","volume":"126","author":"Lee","year":"2012","journal-title":"Circulation"}],"container-title":["Journal of the American College of Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0735109713058683?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0735109713058683?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:12:07Z","timestamp":1564963927000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0735109713058683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":100,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["S0735109713058683"],"URL":"https:\/\/doi.org\/10.1016\/j.jacc.2013.10.025","relation":{},"ISSN":["0735-1097"],"issn-type":[{"value":"0735-1097","type":"print"}],"subject":[],"published":{"date-parts":[[2013,12]]}}}