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Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)\/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH\/5 implantation sites have transcriptomic alterations. Next\u2010generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7.5, revealed complement gene up\u2010regulation in BPH\/5 vs. controls. In BPH\/5, expression of complement factor 3 was increased around the decidual vasculature of E7.5 implantation sites and in the trophoblast giant cell layer of E10.5 placentae. Altered expression of VEGF pathway genes in E5.5 BPH\/5 implantation sites preceded complement dysregulation, which correlated with abnormal vasculature and increased placental growth factor mRNA and VEGF\n                    <jats:sub>164<\/jats:sub>\n                    expression at E7.5. By E10.5, proangiogenic genes were down\u2010regulated, whereas antiangiogenic sFlt\u20101 was up\u2010regulated in BPH\/5 placentae. We found that early local misexpression of VEGF genes and abnormal decidual vasculature precededs Flt\u20101 over expression and increased complement deposition in BPH\/5 placentae. Our findings suggest that abnormal decidual angiogenesis precedes complement activation, which in turn contributes to the aberrant trophoblast invasion and poor placentation that underlie PE.\u2014Sones, J. L., Merriam, A. A., Seffens, A., Brown\u2010Grant, D.\u2010A., Butler, S. D., Zhao, A. M., Xu, X., Shawber, C. J., Grenier, J. K., Douglas, N. C. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH\/5 model of preeclampsia. FASEB J. 32, 2574\u20132586 (2018).\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.201701008r","type":"journal-article","created":{"date-parts":[[2017,12,26]],"date-time":"2017-12-26T12:35:44Z","timestamp":1514291744000},"page":"2574-2586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Angiogenic factor imbalance precedes complement deposition in placentae of the BPH\/5 model of preeclampsia"],"prefix":"10.1096","volume":"32","author":[{"given":"Jennifer L.","family":"Sones","sequence":"first","affiliation":[{"name":"Veterinary Clinical Sciences School of Veterinary Medicine Louisiana State University Baton Rouge Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey A.","family":"Merriam","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Seffens","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dex\u2010Ann","family":"Brown\u2010Grant","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjing","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie J.","family":"Shawber","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Grenier","sequence":"additional","affiliation":[{"name":"RNA Sequencing Core Center for Reproductive Genomics Department of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataki C.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2011.09.011"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000437382.03963.88"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2014.02.001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu018"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.107607"},{"issue":"9","key":"e_1_2_8_7_1","first-page":"S9","article-title":"Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity","volume":"213","author":"Redman C. 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