{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:12:05Z","timestamp":1790179925950,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08HL145132"],"award-info":[{"award-number":["K08HL145132"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL148112"],"award-info":[{"award-number":["R01HL148112"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5P50HD103538"],"award-info":[{"award-number":["5P50HD103538"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS099461"],"award-info":[{"award-number":["R01NS099461"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS110808"],"award-info":[{"award-number":["R01NS110808"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS111230"],"award-info":[{"award-number":["R01NS111230"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS125653"],"award-info":[{"award-number":["R01NS125653"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxia in the neonatal period is associated with early manifestations of adverse cardiovascular health in adulthood including higher risk of hypertension and atherosclerosis. We hypothesize that this occurs due to activation of lysyl oxidases (LOXs) and the remodeling of the large conduit vessels, leading to early arterial stiffening. Newborn C57Bl\/6 mice were exposed to hypoxia (FiO<jats:sub>2<\/jats:sub>\u00a0=\u200911.5%) from postnatal day 1 (P1) to postnatal day 11 (P11), followed by resumption of normoxia. Controls were maintained in normoxia. Using in vivo (pulse wave velocity; PWV) and ex vivo (tensile testing) arterial stiffness indexes, we determined that mice exposed to neonatal hypoxia had significantly higher arterial stiffness compared with normoxia controls by young adulthood (P60), and it increased further by P120. Echocardiography performed at P60 showed that mice exposed to hypoxia displayed a compensated dilated cardiomyopathy. Western blotting revelated that neonatal hypoxia accelerated age\u2010related increase in LOXL2 protein expression in the aorta and elevated LOXL2 expression in the PA at P11 with a delayed decay toward normoxic controls. In the heart and lung, gene and protein expression of LOX\/LOXL2 were upregulated at P11, with a delayed decay when compared to normoxic controls. Neonatal hypoxia results in a significant increase in arterial stiffness in early adulthood due to aberrant LOX\/LOXL2 expression. This suggests an acceleration in the mechanical decline of the cardiovascular system, that contributes to increased risk of hypertension in young adults exposed to neonatal hypoxia that may increase susceptibility to further insults.<\/jats:p>","DOI":"10.14814\/phy2.15656","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T08:14:28Z","timestamp":1681200868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neonatal exposure to hypoxia induces early arterial stiffening via activation of lysyl oxidases"],"prefix":"10.14814","volume":"11","author":[{"given":"Jochen","family":"Steppan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Savage","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rira","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Brady","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bulouere Princess","family":"Wodu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Scafidi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Scafidi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Pediatrics Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Michael V. Johnston Center for Developmental Neuroscience Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-9397","authenticated-orcid":false,"given":"Lakshmi","family":"Santhanam","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Chemical and Biomolecular Engineering Johns Hopkins University School of Medicine, Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.09.015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201302-0302OC"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2020.09.019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2017.08.011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-313296"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2009.41.12.103"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29000"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00141013"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1331"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057454"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.181784"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27695"},{"key":"e_1_2_9_14_1","first-page":"2013","article-title":"Transglutaminase 2 facilitates or ameliorates HIF signaling and ischemic cell death depending on its conformation and localization","volume":"1","author":"Gundemir S.","year":"1833","journal-title":"Biochimica et Biophysica Acta"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487317737174"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210144200"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.540906"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00103.2013"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.273bi.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049321"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200902-0215OC"},{"issue":"290","key":"e_1_2_9_22_1","first-page":"294","article-title":"Dynamic arterial blood gas analysis in conscious, unrestrained C57BL\/6J mice during exposure to intermittent hypoxia","volume":"107","author":"Lee E. J.","year":"2009","journal-title":"Journal of Applied Physiology (1985)"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15574"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.781496"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/HP.S93413"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303534"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2006.04423.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-016-2295-z"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2013-0498"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00128706"},{"key":"e_1_2_9_31_1","first-page":"657","article-title":"The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma","volume":"55","author":"Peng T.","year":"2019","journal-title":"International Journal of Oncology"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.13880"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60136-1"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12880"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.012274"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.110296"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/263585"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004161"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00824"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000599"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2012.04.006"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000001378"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00670.2018"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32833a6132"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00543-8"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02354-0"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0533-1"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8731"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13710"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgt241"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20924107"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T09:29:32Z","timestamp":1703582972000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.15656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.14814\/phy2.15656"],"URL":"https:\/\/doi.org\/10.14814\/phy2.15656","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"2022-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15656"}}