{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:22:33Z","timestamp":1782512553627,"version":"3.54.5"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang Province Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.lfs.2022.121192","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:11:19Z","timestamp":1668391879000},"page":"121192","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":30,"special_numbering":"C","title":["SIRT6 inhibits hypoxia-induced pulmonary arterial smooth muscle cells proliferation via HIF-1\u03b1\/PDK4 signaling"],"prefix":"10.1016","volume":"312","author":[{"given":"Mingxing","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaofa","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglong","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.lfs.2022.121192_bb0005","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.mayocp.2020.04.039","article-title":"Pulmonary hypertension: a brief guide for clinicians","volume":"95","author":"Mandras","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"10.1016\/j.lfs.2022.121192_bb0010","first-page":"243","article-title":"Right heart failure in pulmonary hypertension","volume":"38","author":"Cassady","year":"2020","journal-title":"Cardiol. Clin."},{"key":"10.1016\/j.lfs.2022.121192_bb0015","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":"10.1016\/j.lfs.2022.121192_bb0020","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11886-019-1235-4","article-title":"Pulmonary arterial hypertension: a pharmacotherapeutic update","volume":"21","author":"Coons","year":"2019","journal-title":"Curr. Cardiol. Rep."},{"key":"10.1016\/j.lfs.2022.121192_bb0025","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1097\/HCO.0000000000000796","article-title":"Pharmacologic therapy for pulmonary artery hypertension","volume":"35","author":"Nair","year":"2020","journal-title":"Curr. Opin. Cardiol."},{"key":"10.1016\/j.lfs.2022.121192_bb0030","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":"10.1016\/j.lfs.2022.121192_bb0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.rmed.2020.106099","article-title":"Evaluation and management of pulmonary arterial hypertension","volume":"171","author":"Beshay","year":"2020","journal-title":"Respir. Med."},{"key":"10.1016\/j.lfs.2022.121192_bb0040","doi-asserted-by":"crossref","first-page":"5638","DOI":"10.1172\/JCI137558","article-title":"Hypoxia-inducible factor signaling in pulmonary hypertension","volume":"130","author":"Pullamsetti","year":"2020","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.lfs.2022.121192_bb0045","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1038\/s41467-019-11500-6","article-title":"CD146-HIF-1\u03b1 hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension","volume":"10","author":"Luo","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.lfs.2022.121192_bb0050","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.3892\/mmr.2016.5752","article-title":"Expression and analyses of the HIF-1 pathway in the lungs of humans with pulmonary arterial hypertension","volume":"14","author":"Lei","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.lfs.2022.121192_bb0055","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1165\/rcmb.2020-0023OC","article-title":"Role of hypoxia-inducible factors in regulating right ventricular function and remodeling during chronic hypoxia-induced pulmonary hypertension","volume":"63","author":"Smith","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.lfs.2022.121192_bb0060","first-page":"855","article-title":"Hypoxia promotes pulmonary vascular remodeling via HIF-1\u03b1 to regulate mitochondrial dynamics","volume":"16","author":"Chen","year":"2019","journal-title":"J. Geriatr. Cardiol."},{"key":"10.1016\/j.lfs.2022.121192_bb0065","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cca.2017.01.015","article-title":"Molecular targets of the Warburg effect and inflammatory cytokines in the pathogenesis of pulmonary artery hypertension","volume":"466","author":"Liu","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.lfs.2022.121192_bb0070","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1159\/000479401","article-title":"PDGF promotes the Warburg effect in pulmonary arterial smooth muscle cells via activation of the PI3K\/AKT\/mTOR\/HIF-1\u03b1 signaling pathway","volume":"42","author":"Xiao","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"10.1016\/j.lfs.2022.121192_bb0075","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cca.2016.07.017","article-title":"The Warburg effect: a new story in pulmonary arterial hypertension","volume":"461","author":"Peng","year":"2016","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.lfs.2022.121192_bb0080","first-page":"1391","article-title":"Reversal of the Warburg effect with DCA in PDGF-treated human PASMC is potentiated by pyruvate dehydrogenase kinase-1 inhibition mediated through blocking Akt\/GSK-3\u03b2 signalling","volume":"42","author":"Li","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.lfs.2022.121192_bb0085","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":"10.1016\/j.lfs.2022.121192_bb0090","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1002\/med.21753","article-title":"Emerging roles of SIRT6 in human diseases and its modulators","volume":"41","author":"Liu","year":"2021","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.lfs.2022.121192_bb0095","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1161\/CIRCRESAHA.120.318353","article-title":"SIRT6 protects smooth muscle cells from senescence and reduces atherosclerosis","volume":"128","author":"Grootaert","year":"2021","journal-title":"Circ. Res."},{"key":"10.1016\/j.lfs.2022.121192_bb0100","first-page":"2940","article-title":"SIRT6 overexpression inhibits HIF1\u03b1 expression and its impact on tumor angiogenesis in lung cancer","volume":"11","author":"Wang","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"10.1016\/j.lfs.2022.121192_bb0105","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10863-020-09856-2","article-title":"Downregulation of FOXO6 alleviates hypoxia-induced apoptosis and oxidative stress in cardiomyocytes by enhancing Nrf2 activation via upregulation of SIRT6","volume":"52","author":"Jin","year":"2020","journal-title":"J. Bioenerg. Biomembr."},{"key":"10.1016\/j.lfs.2022.121192_bb0110","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4161\/trns.1.1.12143","article-title":"SIRT6: a master epigenetic gatekeeper of glucose metabolism","volume":"1","author":"Zhong","year":"2010","journal-title":"Transcription"},{"key":"10.1016\/j.lfs.2022.121192_bb0115","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.cell.2009.12.041","article-title":"The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha","volume":"140","author":"Zhong","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.lfs.2022.121192_bb0120","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.cell.2012.10.047","article-title":"The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism","volume":"151","author":"Sebasti\u00e1n","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.lfs.2022.121192_bb0125","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.768513","article-title":"Sanguinarine reverses pulmonary vascular remolding of hypoxia-induced PH via survivin\/HIF1alpha-attenuating kv channels","volume":"12","author":"Fan","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.lfs.2022.121192_bb0130","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1161\/CIRCULATIONAHA.113.004136","article-title":"Heterogeneity in lung: 18FDG uptake in pulmonary arterial hypertension","volume":"128","author":"Zhao","year":"2013","journal-title":"Circulation"},{"key":"10.1016\/j.lfs.2022.121192_bb0135","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1513\/AnnalsATS.201608-605OC","article-title":"Abnormal glucose metabolism and high-energy expenditure in idiopathic pulmonary arterial hypertension","volume":"14","author":"Heresi","year":"2017","journal-title":"Ann. Am. Thorac. So.c"},{"key":"10.1016\/j.lfs.2022.121192_bb0140","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1089\/ars.2018.7657","article-title":"Metabolism and redox in pulmonary vascular physiology and pathophysiology","volume":"31","author":"Alruwaili","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.lfs.2022.121192_bb0145","doi-asserted-by":"crossref","first-page":"13394","DOI":"10.1073\/pnas.1821401116","article-title":"PFKFB3-mediated endothelial glycolysis promotes pulmonary hypertension","volume":"116","author":"Cao","year":"2019","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"10.1016\/j.lfs.2022.121192_bb0150","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1164\/rccm.201812-2290OC","article-title":"PFKFB3 in smooth muscle promotes vascular remodeling in pulmonary arterial hypertension","volume":"200","author":"Kovacs","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.lfs.2022.121192_bb0155","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.mito.2020.11.012","article-title":"Hypoxia-induced mitochondrial reactive oxygen species (mtROS) differentially regulates smooth muscle cell (SMC) proliferation of pulmonary and systemic vasculature","volume":"57","author":"Bhansali","year":"2021","journal-title":"Mitochondrion"},{"key":"10.1016\/j.lfs.2022.121192_bb0160","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.3390\/cancers13051156","article-title":"The two-faced role of SIRT6 in cancer","volume":"13","author":"Fiorentino","year":"2021","journal-title":"Cancers"},{"key":"10.1016\/j.lfs.2022.121192_bb0165","first-page":"728","article-title":"FOXO3a-SIRT6 axis suppresses aerobic glycolysis in melanoma","volume":"56","author":"Dong","year":"2020","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.lfs.2022.121192_bb0170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12272-014-0494-2","article-title":"Role of sirtuins in chronic obstructive pulmonary disease","volume":"38","author":"Chun","year":"2015","journal-title":"Arch. Pharm. Res."},{"key":"10.1016\/j.lfs.2022.121192_bb0175","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1089\/ars.2017.7178","article-title":"SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection","volume":"28","author":"D'Onofrio","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.lfs.2022.121192_bb0180","first-page":"1064","article-title":"SIRT6 protects against endothelial dysfunction and atherosclerosis in mice","volume":"8","author":"Xu","year":"2016","journal-title":"Aging (Albany, NY.)"},{"key":"10.1016\/j.lfs.2022.121192_bb0185","doi-asserted-by":"crossref","first-page":"5703","DOI":"10.3390\/ijms22115703","article-title":"Cancer cell metabolism in hypoxia: role of HIF-1 as key regulator and therapeutic target","volume":"22","author":"Infantino","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.lfs.2022.121192_bb0190","first-page":"521","article-title":"HIF-1: structure, biology and natural modulators","volume":"19","author":"Yang","year":"2021","journal-title":"Chin. J. Nat. Med."},{"key":"10.1016\/j.lfs.2022.121192_bb0195","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.21037\/cdt-20-404","article-title":"Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose\/lipid metabolism","volume":"10","author":"Agrawal","year":"2020","journal-title":"Cardiovasc. Diagn. Therapy"},{"key":"10.1016\/j.lfs.2022.121192_bb0200","doi-asserted-by":"crossref","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":"10.1016\/j.lfs.2022.121192_bb0205","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1038\/s41467-019-10044-z","article-title":"A RASSF1A-HIF1\u03b1 loop drives Warburg effect in cancer and pulmonary hypertension","volume":"10","author":"Dabral","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.lfs.2022.121192_bb0210","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1002\/jcp.26434","article-title":"SIRT6 deacetylase transcriptionally regulates glucose metabolism in heart","volume":"233","author":"Khan","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.lfs.2022.121192_bb0215","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118709","article-title":"Interferon regulatory factor 7 inhibits rat vascular smooth muscle cell proliferation and inflammation in monocrotaline-induced pulmonary hypertension","volume":"264","author":"Deng","year":"2021","journal-title":"Life Sci."},{"key":"10.1016\/j.lfs.2022.121192_bb0220","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3390\/biom10040570","article-title":"Human PCNA structure, function and interactions","volume":"10","author":"Gonzalez-Magana","year":"2020","journal-title":"Biomolecules"},{"key":"10.1016\/j.lfs.2022.121192_bb0225","doi-asserted-by":"crossref","first-page":"240","DOI":"10.2174\/1568009620666200115162814","article-title":"Targeting proliferating cell nuclear antigen (PCNA) as an effective strategy to inhibit tumor cell proliferation","volume":"20","author":"Cardano","year":"2020","journal-title":"Curr. Cancer Drug Targets"},{"key":"10.1016\/j.lfs.2022.121192_bb0230","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/jpi.12184","article-title":"Melatonin attenuates hypoxic pulmonary hypertension by inhibiting the inflammation and the proliferation of pulmonary arterial smooth muscle cells","volume":"57","author":"Jin","year":"2014","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.lfs.2022.121192_bb0235","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BST0380217","article-title":"Regulation of cyclin D1 gene expression","volume":"38","author":"Witzel","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.lfs.2022.121192_bb0240","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109640","article-title":"Osthole inhibits cell proliferation by regulating the TGF-\u03b21\/Smad\/p38 signaling pathways in pulmonary arterial smooth muscle cells","volume":"121","author":"Yue","year":"2020","journal-title":"Biomed. Pharmacother."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002432052200892X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002432052200892X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:03:07Z","timestamp":1758402187000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002432052200892X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":48,"alternative-id":["S002432052200892X"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2022.121192","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"SIRT6 inhibits hypoxia-induced pulmonary arterial smooth muscle cells proliferation via HIF-1\u03b1\/PDK4 signaling","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2022.121192","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"121192"}}