{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:43:11Z","timestamp":1786236191171,"version":"build-2736575974"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170523"],"award-info":[{"award-number":["82170523"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002865","name":"Chongqing Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["CSTB2023NSCQ-BHX0008"],"award-info":[{"award-number":["CSTB2023NSCQ-BHX0008"]}],"id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.ejphar.2026.179123","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:39:34Z","timestamp":1783600774000},"page":"179123","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["GSK484 attenuates placental endothelial injury and improves gestation outcome in rats with preeclampsia by inhibiting PAD4-mediated neutrophil extracellular traps formation"],"prefix":"10.1016","volume":"1030","author":[{"given":"Yuan-Yuan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Fang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Jing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Meng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6546-555X","authenticated-orcid":false,"given":"Ji-Min","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Bin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.ejphar.2026.179123_bib1","first-page":"1","article-title":"ACOG practice bulletin no. 202: gestational hypertension and preeclampsia","volume":"133","year":"2019","journal-title":"Obstet. Gynecol."},{"issue":"23","key":"10.1016\/j.ejphar.2026.179123_bib2","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1007\/s00018-019-03237-8","article-title":"An interplay of structure and intrinsic disorder in the functionality of peptidylarginine deiminases, a family of key autoimmunity-related enzymes","volume":"76","author":"Alghamdi","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.ejphar.2026.179123_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.jri.2024.104237","article-title":"The role of neutrophils and neutrophil extracellular traps (NETs) in stages, outcomes and pregnancy complications","volume":"163","author":"Aslanian-Kalkhoran","year":"2024","journal-title":"J. Reprod. Immunol."},{"issue":"7","key":"10.1016\/j.ejphar.2026.179123_bib4","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0002-9378(85)90676-3","article-title":"Septicemia during pregnancy: a study in different species of experimental animals","volume":"151","author":"Beller","year":"1985","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"5663","key":"10.1016\/j.ejphar.2026.179123_bib5","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.ejphar.2026.179123_bib6","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1161\/HYPERTENSIONAHA.117.10803","article-title":"Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice","volume":"72","author":"Brown","year":"2018","journal-title":"Hypertension"},{"issue":"3","key":"10.1016\/j.ejphar.2026.179123_bib7","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s12022-010-9119-6","article-title":"VEGF and CD31 association in pituitary adenomas","volume":"21","author":"Cristina","year":"2010","journal-title":"Endocr. Pathol."},{"issue":"4","key":"10.1016\/j.ejphar.2026.179123_bib8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41581-022-00670-0","article-title":"The role of immune cells and mediators in preeclampsia","volume":"19","author":"Deer","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"issue":"1","key":"10.1016\/j.ejphar.2026.179123_bib9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41572-023-00417-6","article-title":"Pre-eclampsia","volume":"9","author":"Dimitriadis","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.ejphar.2026.179123_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2019.106055","article-title":"Inhibition of peptidyl arginine deiminase-4 protects against myocardial infarction induced cardiac dysfunction","volume":"78","author":"Du","year":"2020","journal-title":"Int. Immunopharmacol."},{"issue":"6","key":"10.1016\/j.ejphar.2026.179123_bib11","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1095\/biolreprod.116.140293","article-title":"PAD4 deficiency decreases inflammation and susceptibility to pregnancy loss in a mouse model","volume":"95","author":"Erpenbeck","year":"2016","journal-title":"Biol. Reprod."},{"issue":"1","key":"10.1016\/j.ejphar.2026.179123_bib12","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/0002-9378(94)90463-4","article-title":"A new animal model for human preeclampsia: ultra-low-dose endotoxin infusion in pregnant rats","volume":"171","author":"Faas","year":"1994","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"10053","key":"10.1016\/j.ejphar.2026.179123_bib13","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/S0140-6736(16)31575-6","article-title":"Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the global Burden of Disease Study 2015","volume":"388","year":"2016","journal-title":"Lancet"},{"issue":"10053","key":"10.1016\/j.ejphar.2026.179123_bib14","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/S0140-6736(16)31470-2","article-title":"Global, regional, and national levels of maternal mortality, 1990-2015: a systematic analysis for the global burden of disease study 2015","volume":"388","year":"2016","journal-title":"Lancet"},{"issue":"12","key":"10.1016\/j.ejphar.2026.179123_bib15","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1161\/CIRCRESAHA.124.325673","article-title":"Overload of neprilysin in placental extracellular vesicles disrupts CNP-NPRB-mediated communication between vascular endothelial and smooth muscle cells: a trigger for symptoms of preeclampsia","volume":"136","author":"He","year":"2025","journal-title":"Circ. Res."},{"issue":"5","key":"10.1016\/j.ejphar.2026.179123_bib16","doi-asserted-by":"crossref","first-page":"605","DOI":"10.3390\/ph17050605","article-title":"Targeting neutrophil extracellular trap formation: exploring promising pharmacological strategies for the treatment of preeclampsia","volume":"17","author":"Hern\u00e1ndez Gonz\u00e1lez","year":"2024","journal-title":"Pharmaceuticals"},{"issue":"1","key":"10.1016\/j.ejphar.2026.179123_bib17","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1152\/physrev.00062.2021","article-title":"Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases","volume":"103","author":"Herre","year":"2023","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejphar.2026.179123_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2021.102051","article-title":"Nox2 impairs VEGF-A-induced angiogenesis in placenta via mitochondrial ROS-STAT3 pathway","volume":"45","author":"Hu","year":"2021","journal-title":"Redox Biol."},{"issue":"12","key":"10.1016\/j.ejphar.2026.179123_bib19","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1055\/s-0038-1675788","article-title":"Increased neutrophil activation and plasma DNA levels in patients with pre-eclampsia","volume":"118","author":"Hu","year":"2018","journal-title":"Thromb. Haemost."},{"issue":"7","key":"10.1016\/j.ejphar.2026.179123_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.107162","article-title":"Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis","volume":"26","author":"Hu","year":"2023","journal-title":"iScience"},{"issue":"6","key":"10.1016\/j.ejphar.2026.179123_bib21","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3390\/biom10060953","article-title":"Pathogenesis of Preeclampsia and therapeutic approaches targeting the placenta","volume":"10","author":"Jena","year":"2020","journal-title":"Biomolecules"},{"key":"10.1016\/j.ejphar.2026.179123_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110122","article-title":"The bioflavonoid quercetin improves pathophysiology in a rat model of preeclampsia","volume":"127","author":"Li","year":"2020","journal-title":"Biomed. Pharmacother."},{"issue":"8029","key":"10.1016\/j.ejphar.2026.179123_bib23","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41586-024-07820-3","article-title":"Recognition and control of neutrophil extracellular trap formation by MICL","volume":"633","author":"Malamud","year":"2024","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.ejphar.2026.179123_bib24","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/HYPERTENSIONAHA.120.14974","article-title":"Affinity-enhanced multimeric VEGF (vascular endothelial growth factor) and PlGF (placental growth factor) variants for specific adsorption of sFlt-1 to restore angiogenic balance in preeclampsia","volume":"76","author":"Matin","year":"2020","journal-title":"Hypertension"},{"issue":"3","key":"10.1016\/j.ejphar.2026.179123_bib25","doi-asserted-by":"crossref","DOI":"10.1111\/micc.12352","article-title":"Neutrophil-mediated vascular barrier injury: role of neutrophil extracellular traps","volume":"24","author":"Meegan","year":"2017","journal-title":"Microcirculation"},{"issue":"12","key":"10.1016\/j.ejphar.2026.179123_bib26","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1096\/fj.201700399RR","article-title":"Neutrophil extracellular traps are critical for pregnancy loss in sphingosine kinase-deficient mice on 129Sv\/C57BL\/6 background","volume":"31","author":"Mizugishi","year":"2017","journal-title":"FASEB J."},{"issue":"13","key":"10.1016\/j.ejphar.2026.179123_bib27","first-page":"2652","article-title":"Targeted delivery of protein arginine deiminase-4 inhibitors to limit arterial intimal NETosis and preserve endothelial integrity","volume":"117","author":"Molinaro","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ejphar.2026.179123_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.112861","article-title":"Peptidyl arginine deiminase-4 inhibitor ameliorates pulmonary fibrosis through positive regulation of developmental endothelial locus-1","volume":"140","author":"Panda","year":"2024","journal-title":"Int. Immunopharmacol."},{"issue":"2","key":"10.1016\/j.ejphar.2026.179123_bib29","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil extracellular traps in immunity and disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat. Rev. Immunol."},{"issue":"5","key":"10.1016\/j.ejphar.2026.179123_bib30","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41581-019-0119-6","article-title":"Pre-eclampsia: pathogenesis, novel diagnostics and therapies","volume":"15","author":"Phipps","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.ejphar.2026.179123_bib31","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1488127","article-title":"Circulating extracellular vesicles and neutrophil extracellular traps contribute to endothelial dysfunction in preeclampsia","volume":"15","author":"Ramos","year":"2024","journal-title":"Front. Immunol."},{"issue":"1\u20132","key":"10.1016\/j.ejphar.2026.179123_bib32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jri.2013.05.003","article-title":"If we know so much about preeclampsia, why haven't we cured the disease","volume":"99","author":"Roberts","year":"2013","journal-title":"J. Reprod. Immunol."},{"key":"10.1016\/j.ejphar.2026.179123_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.reprotox.2023.108405","article-title":"Exposure to valproic acid (VPA) resulted in alterations in the expression of angiogenic genes (NRP-1, VEGFA, VEGFR-2 and sFlt 1) and histological modifications in the placenta of mice (Mus musculus)","volume":"119","author":"Ruyani","year":"2023","journal-title":"Reprod. Toxicol."},{"issue":"12","key":"10.1016\/j.ejphar.2026.179123_bib34","first-page":"2396","article-title":"[GSK484, a PAD4 inhibitor, improves endothelial dysfunction in mice with sepsis-induced lung injury by inhibiting H3Cit expression]","volume":"44","author":"Su","year":"2024","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"issue":"10","key":"10.1016\/j.ejphar.2026.179123_bib35","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.147564","article-title":"NETosis in the pathogenesis of acute lung injury following cutaneous chemical burns","volume":"6","author":"Surolia","year":"2021","journal-title":"JCI Insight"},{"issue":"8045","key":"10.1016\/j.ejphar.2026.179123_bib36","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41586-024-08291-2","article-title":"Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia","volume":"637","author":"Swingle","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2026.179123_bib37","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/8238727","article-title":"Cross-talk between oxidative stress and inflammation in preeclampsia","volume":"2019","author":"Ten\u00f3rio","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.ejphar.2026.179123_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.jri.2021.103306","article-title":"Polymicrobial stimulation of human fetal membranes induce neutrophil activation and neutrophil extracellular trap release","volume":"145","author":"Tong","year":"2021","journal-title":"J. Reprod. Immunol."},{"issue":"6","key":"10.1016\/j.ejphar.2026.179123_bib39","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/s41423-024-01158-6","article-title":"Neutrophil-derived PAD4 induces citrullination of CKMT1 exacerbates mucosal inflammation in inflammatory bowel disease","volume":"21","author":"Wang","year":"2024","journal-title":"Cell. Mol. Immunol."},{"issue":"2","key":"10.1016\/j.ejphar.2026.179123_bib40","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1083\/jcb.200806072","article-title":"Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation","volume":"184","author":"Wang","year":"2009","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.ejphar.2026.179123_bib41","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.placenta.2024.05.136","article-title":"The protective mechanism of human umbilical cord mesenchymal stem cell-derived exosomes against neutrophil extracellular trap-induced placental damage","volume":"153","author":"Wang","year":"2024","journal-title":"Placenta"},{"key":"10.1016\/j.ejphar.2026.179123_bib42","first-page":"l5119","article-title":"Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance","volume":"366","author":"Webster","year":"2019","journal-title":"Br. Med. J. (Pract. Obs. Ed.)"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299926006059?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299926006059?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:29:58Z","timestamp":1786235398000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299926006059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":42,"alternative-id":["S0014299926006059"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2026.179123","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"GSK484 attenuates placental endothelial injury and improves gestation outcome in rats with preeclampsia by inhibiting PAD4-mediated neutrophil extracellular traps formation","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2026.179123","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"179123"}}