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However, the underlying mechanism by which EPE affects the maternal brain is not known. We hypothesized that plasma from women with EPE increases blood\u2010brain barrier (BBB) permeability\n                    <jats:italic>vs.<\/jats:italic>\n                    plasma from women with late\u2010onset preeclampsia (LPE) or normal pregnancy (NP) and investigated its underlying mechanism by perfusing cerebral veins from nonpregnant rats (\n                    <jats:italic>n<\/jats:italic>\n                    =6\u20137\/group) with human plasma from women with EPE, LPE, or NP and measuring permeability. We show that plasma from women with EPE significantly increased BBB permeability\n                    <jats:italic>vs.<\/jats:italic>\n                    plasma from women with LPE or NP (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001). BBB disruption in response to EPE plasma was due to a 260% increase of circulating oxidized LDL (oxLDL) binding to its receptor, LOX\u20101, and subsequent generation of peroxynitrite (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001). A rat model with pathologically high lipid levels in pregnancy showed symptoms of preeclampsia, including elevated blood pressure, growth\u2010restricted fetuses, and LOX\u20101\u2010dependent BBB disruption, similar to EPE (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). Thus, we have identified LOX\u20101 activation by oxLDL and subsequent peroxynitrite generation as a novel mechanism by which disruption of the BBB occurs in EPE. As increased BBB permeability is a primary means by which seizure and other neurological symptoms ensue, our findings highlight oxLDL, LOX\u20101, and peroxynitrite as important therapeutic targets in EPE.\u2014Schreurs, M. P. H., Hubel, C. A., Bernstein, I. M., Jeyabalan, A., and Cipolla, M. J. Increased oxidized low\u2010density lipoprotein causes blood\u2010brain barrier disruption in early\u2010onset preeclampsia through LOX\u20101.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 1254\u20131263 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-222216","type":"journal-article","created":{"date-parts":[[2012,12,10]],"date-time":"2012-12-10T22:48:06Z","timestamp":1355179686000},"page":"1254-1263","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Increased oxidized low\u2010density lipoprotein causes blood\u2010brain barrier disruption in early\u2010onset preeclampsia through LOX\u20101"],"prefix":"10.1096","volume":"27","author":[{"given":"Malou P. H.","family":"Schreurs","sequence":"first","affiliation":[{"name":"Department of Neurology University of Vermont College of Medicine Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl A.","family":"Hubel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences University of Pittsburgh Pittsburgh Pennsylvania USA"},{"name":"Magee\u2010Womens Research Institute University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira M.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences University of Vermont College of Medicine Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Jeyabalan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences University of Pittsburgh Pittsburgh Pennsylvania USA"},{"name":"Magee\u2010Womens Research Institute University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn J.","family":"Cipolla","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Vermont College of Medicine Burlington Vermont USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences University of Vermont College of Medicine Burlington Vermont USA"},{"name":"Department of Pharmacology University of Vermont College of Medicine Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2009.02.010"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2009.02.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7292(00)00295-2"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpm.2011.098"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.309.6966.1395"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1081\/PRG-120021060"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1067\/S0002-9378(03)00651-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.106.079442"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002340000439"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.03.005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijgo.2005.09.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.158931"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(98)90337-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.atherosclerosis.2005.06.028","article-title":"Oxidized\u2010LDL levels in normal and pre\u2010eclamptic pregnancies: contribution of LDL particle size","volume":"183","author":"Belo L.","year":"2005","journal-title":"Atherosclerosis"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.33549\/physiolres.930813","article-title":"Oxidized low\u2010density lipoprotein (oxidized LDL) and the risk of preeclampsia","volume":"55","author":"Qiu C.","year":"2006","journal-title":"Physiol. 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