{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:29:38Z","timestamp":1777390178962,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>High\u2010altitude pulmonary oedema (HAPE) is a non\u2010cardiogenic pulmonary oedema that can occur during rapid ascent to a high\u2010altitude environment. Classically, HAPE has been described as a condition resulting from a combination of pulmonary vasoconstriction and hypertension. Inflammation has been described as important in HAPE, although as a side effect of pulmonary oedema rather than as a causative factor. In this study, we aim to understand the role of hypoxic response in myeloid cells and its involvement in pathogenesis of HAPE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have generated a conditional deletion in mice of the von Hippel\u2010Lindau factor (VHL) in myeloid cells to determine the effect of a deregulated hypoxic response in pulmonary oedema.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The deletion of VHL in pulmonary myeloid cells gave rise to pulmonary oedema, increased pulmonary vascular permeability and reduced performance during exertion. These changes were accompanied by reduced stroke volume in the left ventricle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this model, we show that a deregulated myeloid cell hypoxic response can trigger some of the most important symptoms of HAPE, and thus mice with a deletion of VHL in the myeloid lineage can function as a model of HAPE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13461","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T14:11:10Z","timestamp":1583331070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Deregulated hypoxic response in myeloid cells: A model for high\u2010altitude pulmonary oedema (HAPE)"],"prefix":"10.1111","volume":"229","author":[{"given":"Milos","family":"Gojkovic","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology Karolinska Institute Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella S.","family":"Darmasaputra","sequence":"additional","affiliation":[{"name":"University of Utrecht Faculty of Medicine \u2010 Cancer Biology Utrecht Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Veli\u00e7a","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology Karolinska Institute Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene","family":"Rundqvist","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institute Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4084-6639","authenticated-orcid":false,"given":"Randall S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology Karolinska Institute Stockholm Sweden"},{"name":"Department of Physiology Development and Neuroscience University of Cambridge Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"155","article-title":"Pulmonary edema: pathophysiology and diagnosis","volume":"15","author":"Murray JF","year":"2011","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc2906"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01201.2001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.128581"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5278.107066"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2010.02.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2010.03.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1580\/07-WEME-REV-173.1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01167.2004"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-145-7-200610030-00007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(98)00006-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)80033-9"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.12.1124"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-015-0491-3"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.978627"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.021"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.250167.114"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2018.12.001"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00154-5"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1881410"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01624"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.008"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06905"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103377"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10138"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07445"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01530.x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00292"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707494"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7993"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.155788"},{"key":"e_1_2_10_34_1","first-page":"54","article-title":"Regulation of cell adhesion by PAI\u20101","volume":"107","author":"Loskutoff DJ","year":"1999","journal-title":"AMPIS"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600871RR"},{"key":"e_1_2_10_36_1","first-page":"5587","article-title":"Plasminogen activator inhibitor\u20101 promotes angiogenesis by stimulating endothelial cell migration toward fibronectin","volume":"61","author":"Isogai C","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.121.6.1433"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapha.13461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.13461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T09:10:12Z","timestamp":1693991412000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.13461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,16]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1111\/apha.13461"],"URL":"https:\/\/doi.org\/10.1111\/apha.13461","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,16]]},"assertion":[{"value":"2019-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13461"}}