{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:21:40Z","timestamp":1788916900712,"version":"build-2803163510"},"reference-count":70,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD088590"],"award-info":[{"award-number":["HD088590"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL138181"],"award-info":[{"award-number":["HL138181"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The environmental hypoxia of high altitude (HA) increases the incidence of intrauterine growth restriction (IUGR) approximately threefold. The peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u2010\u03b3), a ligand\u2010activated nuclear receptor that promotes vasorelaxation by increasing nitric oxide and downregulating endothelin\u20101 (ET\u20101) production, has been implicated in IUGR. Based on our prior work indicating that pharmacologic activation of the PPAR\u03b3 pathway protects against hypoxia\u2010associated IUGR, we used an experimental murine model to determine whether such effects may be attributed to vasodilatory effects in the uteroplacental circulation. Using wire myography, ex vivo vasoreactivity studies were conducted in uterine arteries (UtA) isolated from pregnant mice exposed to hypoxia or normoxia from gestational day 14.5 to 18.5. Exposure to troglitazone, a high\u2010affinity PPAR\u03b3 agonist\u2010induced vasorelaxation in UtA preconstricted with phenylephrine, with HA\u2010UtA showing increased sensitivity. Troglitazone blunted ET\u20101\u2010induced contraction of UtA in hypoxic and normoxic dams equivalently. Immunohistological analysis revealed enhanced staining for ET\u20101 receptors in the placental labyrinthine zone in hypoxic compared to normoxic dams. Our results suggest that pharmacologic PPAR\u2010\u03b3 activation, via its vasoactive properties, may protect the fetal growth under hypoxic conditions by improving uteroplacental perfusion and thereby justify further investigation into PPAR\u03b3 as a therapeutic target for IUGR in pregnancies complicated by hypoxia.<\/jats:p>","DOI":"10.1096\/fj.201902264rr","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T03:44:16Z","timestamp":1579751056000},"page":"4283-4292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Peroxisome proliferator\u2010activated receptor gamma blunts endothelin\u20101\u2010mediated contraction of the uterine artery in a murine model of high\u2010altitude pregnancy"],"prefix":"10.1096","volume":"34","author":[{"given":"Sydney L.","family":"Lane","sequence":"first","affiliation":[{"name":"Integrated Physiology Program University of Colorado Graduate School Aurora CO USA"},{"name":"Department of Obstetrics and Gynecology University of Colorado School of Medicine Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandrea S.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Colorado Mesa University Grand Junction CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise S.","family":"Bales","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Colorado School of Medicine Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Houck","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Colorado Mesa University Grand Junction CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n A.","family":"Lorca","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Colorado School of Medicine Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna G.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Colorado School of Medicine Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen G.","family":"Julian","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado School of Medicine Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.384"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.12314"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-2343"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.87.6.1003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1957.02060040668009"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1988.03720230037027"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.109579"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12080"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0068"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.79.1.7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00164.2008"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.91046.2008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-0528.2003.t01-1-02163.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3159"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008055"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.10.3874"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.179440"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00184"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.025031"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.5.394"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000177805.65864.d4"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00148.2009"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/142082"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.04.009"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00062.2011"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa5038"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0849"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.10.3808"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1064"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-239749"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900214R"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.28.917"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1155\/PPAR\/2006\/73986"},{"key":"e_1_2_9_35_1","unstructured":"National Research Council.Guide for the Care and Use of Laboratory Animals.8th ed..Washington DC:The National Academies Press;2011."},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nrendo.2015.101","article-title":"PPAR agonists in pre\u2010eclampsia and hypertension?","volume":"11","author":"Geach T","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506930"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00164.2008"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01449"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1556\/036.102.2015.4.6","article-title":"The effect of high altitude on endothelial and vascular dysfunction markers in preeclamptic patients","volume":"102","author":"Bashir SO","year":"2015","journal-title":"Acta Physiol Hung"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000103"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2003.008"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000292386"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsgi.2003.07.001"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200212000-00003"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00603.2012"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0337OC"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.6.H2069"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00119.2016"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00701.2002"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.12641"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1216-4"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13224-011-0092-x"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2000.0535"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-68-3-676"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(93)90027-G"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(85)80223-4"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.6.1888"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/34178"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/34184"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.05.005"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00131-4"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0596"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/PPAR\/2006\/73986"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2012.691963"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000256090.42690.05"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20920"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.03.012"},{"key":"e_1_2_9_69_1","doi-asserted-by":"crossref","first-page":"12650","DOI":"10.1038\/srep12650","article-title":"PPARgamma stimulates expression of L\u2010type amino acid and taurine transporters in human placentas: the evidence of PPARgamma regulating fetal growth","volume":"5","author":"Chen Z","year":"2015","journal-title":"Sci Rep"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202489200"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505649200"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffj.201902264RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201902264RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201902264RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201902264RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T12:35:17Z","timestamp":1762086917000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201902264RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,23]]},"references-count":70,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1096\/fj.201902264RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.201902264rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,23]]},"assertion":[{"value":"2019-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}