{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:08:45Z","timestamp":1790510925006,"version":"4.1.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0220490","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T17:43:02Z","timestamp":1564594982000},"page":"e0220490","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Alterations in platelet bioenergetics in Group 2 PH-HFpEF patients"],"prefix":"10.1371","volume":"14","author":[{"given":"Quyen L.","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinna","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Helbling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-2113","authenticated-orcid":true,"given":"Sruti","family":"Shiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"issue":"25 Suppl","key":"ref1","doi-asserted-by":"crossref","first-page":"D1","DOI":"10.1016\/j.jacc.2013.10.030","article-title":"The Fifth World Symposium on Pulmonary Hypertension","volume":"62","author":"N Galie","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biocel.2014.08.012","article-title":"Mitochondria: roles in pulmonary hypertension","volume":"55","author":"V Freund-Michel","year":"2014","journal-title":"Int J Biochem Cell Biol"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1161\/CIRCRESAHA.115.301130","article-title":"The metabolic theory of pulmonary arterial hypertension","volume":"115","author":"R Paulin","year":"2014","journal-title":"Circ Res"},{"issue":"44","key":"ref4","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":"G Sutendra","year":"2010","journal-title":"Sci Transl Med"},{"issue":"4","key":"ref5","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":"W Xu","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"ref6","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00109-010-0670-x","article-title":"The role of mitochondria in pulmonary vascular remodeling","volume":"88","author":"P Dromparis","year":"2010","journal-title":"J Mol Med (Berl)"},{"issue":"8","key":"ref7","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":"MS McMurtry","year":"2004","journal-title":"Circ Res"},{"issue":"22","key":"ref8","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1161\/CIRCULATIONAHA.105.609008","article-title":"An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension","volume":"113","author":"S Bonnet","year":"2006","journal-title":"Circulation"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCHEARTFAILURE.111.966127","article-title":"Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension","volume":"6","author":"J Gomez-Arroyo","year":"2013","journal-title":"Circ Heart Fail"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"L435","DOI":"10.1152\/ajplung.00169.2015","article-title":"Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake","volume":"309","author":"BB Graham","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00109-011-0804-9","article-title":"Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle&apos;s cycle","volume":"90","author":"YH Fang","year":"2012","journal-title":"J Mol Med (Berl)"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00109-009-0524-6","article-title":"The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: resuscitating the hibernating right ventricle","volume":"88","author":"L Piao","year":"2010","journal-title":"J Mol Med (Berl)"},{"issue":"11","key":"ref13","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00109-013-1059-4","article-title":"A metabolic 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":"G Sutendra","year":"2013","journal-title":"J Mol Med (Berl)"},{"issue":"4","key":"ref14","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.cardiores.2007.05.012","article-title":"Right-ventricular failure is associated with increased mitochondrial complex II activity and production of reactive oxygen species","volume":"75","author":"EM Redout","year":"2007","journal-title":"Cardiovasc Res"},{"issue":"5","key":"ref15","doi-asserted-by":"crossref","first-page":"e91415","DOI":"10.1172\/jci.insight.91415","article-title":"Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity","volume":"2","author":"QL Nguyen","year":"2017","journal-title":"JCI Insight"},{"issue":"8","key":"ref16","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1161\/CIRCULATIONAHA.111.085761","article-title":"Pulmonary hypertension due to left heart disease","volume":"126","author":"M Guazzi","year":"2012","journal-title":"Circulation"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/eurjhf\/hfq121","article-title":"Epidemiology and clinical course of heart failure with preserved ejection fraction","volume":"13","author":"CS Lam","year":"2011","journal-title":"Eur J Heart Fail"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1161\/01.CIR.0000111245.75752.C6","article-title":"Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute\/American Heart Association conference on scientific issues related to definition","volume":"109","author":"SM Grundy","year":"2004","journal-title":"Circulation"},{"issue":"39","key":"ref19","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1093\/eurheartj\/ehv350","article-title":"The role of metabolic syndrome in heart failure","volume":"36","author":"P Perrone-Filardi","year":"2015","journal-title":"Eur Heart J"},{"issue":"25 Suppl","key":"ref20","doi-asserted-by":"crossref","first-page":"D100","DOI":"10.1016\/j.jacc.2013.10.033","article-title":"Pulmonary hypertension due to left heart diseases","volume":"62","author":"JL Vachiery","year":"2013","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"ref21","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1183\/13993003.01032-2015","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"46","author":"N Galie","year":"2015","journal-title":"Eur Respir J"},{"issue":"18","key":"ref22","doi-asserted-by":"crossref","first-page":"e89620","DOI":"10.1172\/jci.insight.89620","article-title":"Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction","volume":"1","author":"MA Simon","year":"2016","journal-title":"JCI Insight"},{"issue":"18","key":"ref23","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1182\/blood-2013-09-529420","article-title":"Platelet bioenergetic screen in sickle cell patients reveals mitochondrial complex V inhibition, which contributes to platelet activation","volume":"123","author":"N Cardenes","year":"2014","journal-title":"Blood"},{"issue":"7","key":"ref24","doi-asserted-by":"crossref","first-page":"e0132007","DOI":"10.1371\/journal.pone.0132007","article-title":"Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis","volume":"10","author":"W Xu","year":"2015","journal-title":"PLoS One"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1471-2407-11-56","article-title":"Establishing a relationship between prolactin and altered fatty acid beta-oxidation via carnitine palmitoyl transferase 1 in breast cancer cells","volume":"11","author":"K Linher-Melville","year":"2011","journal-title":"BMC Cancer"},{"issue":"9","key":"ref26","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1084\/jem.20070198","article-title":"Nitrite augments tolerance to ischemia\/reperfusion injury via the modulation of mitochondrial electron transfer","volume":"204","author":"S Shiva","year":"2007","journal-title":"J Exp Med"},{"issue":"1","key":"ref27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10020-018-0005-x","article-title":"Uncoupling of glycolysis from glucose oxidation accompanies the development of heart failure with preserved ejection fraction","volume":"24","author":"N Fillmore","year":"2018","journal-title":"Mol Med"},{"issue":"13","key":"ref28","doi-asserted-by":"crossref","first-page":"15410","DOI":"10.18632\/oncotarget.7645","article-title":"Reprogramming of energy metabolism as a driver of aging","volume":"7","author":"Z Feng","year":"2016","journal-title":"Oncotarget"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/srep00134","article-title":"The metabolic footprint of aging in mice","volume":"1","author":"RH Houtkooper","year":"2011","journal-title":"Sci Rep"},{"issue":"2","key":"ref30","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0735-1097(02)02714-6","article-title":"Impact of aging on substrate metabolism by the human heart","volume":"41","author":"AM Kates","year":"2003","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/cphy.c140041","article-title":"Metabolic shifts during aging and pathology","volume":"5","author":"Y Ma","year":"2015","journal-title":"Compr Physiol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e1835","DOI":"10.1038\/cddis.2015.202","article-title":"Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival","volume":"6","author":"J Pfleger","year":"2015","journal-title":"Cell Death Dis"},{"key":"ref33","article-title":"Bioenergetic Differences in the Airway Epithelium of Lean Versus Obese Asthmatics Are Driven by Nitric Oxide and Reflected in Circulating Platelets","author":"D Winnica","year":"2019","journal-title":"Antioxid Redox Signal"},{"issue":"2","key":"ref34","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0012-3692(15)51873-4","article-title":"Thrombotic arteriopathy and anticoagulation in pulmonary hypertension","volume":"130","author":"SR Johnson","year":"2006","journal-title":"Chest"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2119\/molmed.2013.00165","article-title":"Molecular mechanisms of pulmonary arterial remodeling","volume":"20","author":"P Crosswhite","year":"2014","journal-title":"Mol Med"},{"issue":"2","key":"ref36","first-page":"145","article-title":"Platelets in pulmonary hypertension: a causative role or a simple association?","volume":"22","author":"KS Zanjani","year":"2012","journal-title":"Iran J Pediatr"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1467-789X.2011.00930.x","article-title":"Platelet activation in obesity and metabolic syndrome","volume":"13","author":"F Santilli","year":"2012","journal-title":"Obes Rev"},{"issue":"3","key":"ref38","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/ajh.2009.247","article-title":"Platelet activation in essential hypertension: implications for antiplatelet treatment","volume":"23","author":"E Gkaliagkousi","year":"2010","journal-title":"Am J Hypertens"},{"key":"ref39","first-page":"501","article-title":"Platelet hemostasis in patients with metabolic syndrome and type 2 diabetes mellitus: cGMP- and NO-dependent mechanisms in the insulin-mediated platelet aggregation","volume":"5","author":"TE Suslova","year":"2014","journal-title":"Front Physiol"},{"issue":"2","key":"ref40","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11906-017-0710-9","article-title":"Role of Mitochondrial Dysfunction in Hypertension and Obesity","volume":"19","author":"V Lahera","year":"2017","journal-title":"Curr Hypertens Rep"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/EC-14-0092","article-title":"Mitochondrial dysfunction and insulin resistance: an update","volume":"4","author":"MK Montgomery","year":"2015","journal-title":"Endocr Connect"},{"issue":"5","key":"ref42","doi-asserted-by":"crossref","first-page":"343","DOI":"10.7326\/0003-4819-115-5-343","article-title":"Survival in patients with primary pulmonary hypertension. Results from a national prospective registry","volume":"115","author":"GE D'Alonzo","year":"1991","journal-title":"Ann Intern Med"},{"issue":"24","key":"ref43","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1016\/j.jacc.2011.06.068","article-title":"Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy","volume":"58","author":"MC van de Veerdonk","year":"2011","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"ref44","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1161\/CIRCULATIONAHA.109.887570","article-title":"Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure","volume":"121","author":"P Meyer","year":"2010","journal-title":"Circulation"},{"issue":"12","key":"ref45","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1002\/ejhf.630","article-title":"Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis","volume":"18","author":"TM Gorter","year":"2016","journal-title":"Eur J Heart Fail"},{"issue":"25","key":"ref46","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1161\/CIRCULATIONAHA.113.008461","article-title":"Right ventricular function in heart failure with preserved ejection fraction: a community-based study","volume":"130","author":"SF Mohammed","year":"2014","journal-title":"Circulation"},{"issue":"3","key":"ref47","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1086\/674326","article-title":"Shorter survival in familial versus idiopathic pulmonary arterial hypertension is associated with hemodynamic markers of impaired right ventricular function","volume":"3","author":"EL Brittain","year":"2013","journal-title":"Pulm Circ"},{"issue":"4","key":"ref48","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jchf.2013.05.004","article-title":"Prostanoids but not oral therapies improve right ventricular function in pulmonary arterial hypertension","volume":"1","author":"EL Brittain","year":"2013","journal-title":"JACC Heart Fail"},{"issue":"11","key":"ref49","doi-asserted-by":"crossref","first-page":"H2148","DOI":"10.1152\/ajpheart.00907.2011","article-title":"Inflammation and metabolic dysfunction: links to cardiovascular diseases","volume":"302","author":"A Taube","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"6","key":"ref50","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.tcb.2017.01.006","article-title":"Inflammation and the Metabolic Syndrome: The Tissue-Specific Functions of NF-kappaB","volume":"27","author":"L Catrysse","year":"2017","journal-title":"Trends Cell Biol"},{"issue":"4","key":"ref51","doi-asserted-by":"crossref","first-page":"397","DOI":"10.2174\/1573399810602040397","article-title":"The role of adipocytokines and neurohormonal dysregulation in metabolic syndrome","volume":"2","author":"AP Kong","year":"2006","journal-title":"Curr Diabetes Rev"},{"issue":"4","key":"ref52","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jacc.2013.02.092","article-title":"A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation","volume":"62","author":"WJ Paulus","year":"2013","journal-title":"J Am Coll Cardiol"},{"issue":"8","key":"ref53","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1161\/CIRCULATIONAHA.115.018935","article-title":"SIRT3-AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction","volume":"133","author":"YC Lai","year":"2016","journal-title":"Circulation"},{"issue":"1","key":"ref54","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.redox.2012.11.005","article-title":"Nitrite: A Physiological Store of Nitric Oxide and Modulator of Mitochondrial Function","volume":"1","author":"S Shiva","year":"2013","journal-title":"Redox Biol"},{"issue":"2","key":"ref55","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.pharmthera.2007.06.012","article-title":"Impaired tissue responsiveness to organic nitrates and nitric oxide: a new therapeutic frontier?","volume":"116","author":"YY Chirkov","year":"2007","journal-title":"Pharmacol Ther"},{"issue":"1","key":"ref56","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S1388-9842(03)00038-2","article-title":"Determinants of platelet responsiveness to nitric oxide in patients with chronic heart failure","volume":"6","author":"RA Anderson","year":"2004","journal-title":"Eur J Heart Fail"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ijcard.2014.10.137","article-title":"Impaired platelet nitric oxide response in patients with new onset atrial fibrillation","volume":"179","author":"NE Procter","year":"2015","journal-title":"Int J Cardiol"},{"issue":"3","key":"ref58","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10557-008-6098-7","article-title":"Platelet hyperaggregability: impaired responsiveness to nitric oxide (&quot;platelet NO resistance&quot;) as a therapeutic target","volume":"22","author":"S Rajendran","year":"2008","journal-title":"Cardiovasc Drugs Ther"},{"issue":"9","key":"ref59","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/0002-9149(94)90583-5","article-title":"Alterations in nitric oxide synthase activity, superoxide anion generation, and platelet aggregation in systemic hypertension, and effects of celiprolol","volume":"74","author":"JL Mehta","year":"1994","journal-title":"Am J Cardiol"},{"issue":"35","key":"ref60","doi-asserted-by":"crossref","first-page":"14362","DOI":"10.1074\/jbc.M117.787390","article-title":"Guanylyl cyclase sensitivity to nitric oxide is protected by a thiol oxidation-driven interaction with thioredoxin-1","volume":"292","author":"C Huang","year":"2017","journal-title":"J Biol Chem"},{"issue":"3","key":"ref61","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1089\/ars.2015.6591","article-title":"Thiol-Based Redox Modulation of Soluble Guanylyl Cyclase, the Nitric Oxide Receptor","volume":"26","author":"A Beuve","year":"2017","journal-title":"Antioxid Redox Signal"},{"issue":"12","key":"ref62","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1161\/01.ATV.0000193622.77294.57","article-title":"Platelet nitric oxide responsiveness: a novel prognostic marker in acute coronary syndromes","volume":"25","author":"SR Willoughby","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0220490","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T03:21:18Z","timestamp":1588994478000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0220490"}},"subtitle":[],"editor":[{"given":"Jianhua","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,7,31]]},"references-count":62,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0220490","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,31]]}}}