{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:20:59Z","timestamp":1787721659149,"version":"build-2784847793"},"reference-count":106,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pre\u2010eclampsia is a complex multisystem hypertensive disorder of pregnancy and a leading cause of maternal and perinatal morbidity and mortality worldwide. Increasing evidence suggests that the condition extends beyond abnormal placentation and represents an integrated immuno\u2010cardiovascular disorder characterized by immune dysregulation, endothelial dysfunction, thromboinflammation, and cardiovascular maladaptation. This narrative review examines the interconnected mechanisms linking cytokine\u2010mediated inflammation, endothelial injury, coagulation abnormalities, and maternal cardiovascular instability in pre\u2010eclampsia. A structured literature search of major biomedical databases was conducted to identify relevant experimental, clinical, and translational studies addressing inflammatory cytokines, angiogenic imbalance, endothelial dysfunction, thrombosis, biomarkers, and therapeutic strategies in pre\u2010eclampsia. The review highlights the central roles of pro\u2010inflammatory mediators, including tumor necrosis factor\u2010\u03b1, interleukin\u20106, interleukin\u201017, and interferon\u2010\u03b3, in promoting oxidative stress, vascular inflammation, and endothelial dysfunction. Particular attention is given to the development of an immunothrombotic environment, defined as the pathological interaction between immune activation and coagulation pathways that promotes thrombosis and vascular injury. The review also critically evaluates the contribution of antiangiogenic factors, platelet activation, impaired fibrinolysis, and cardiovascular remodeling to maternal disease progression. In addition, current and emerging therapeutic approaches targeting inflammatory, endothelial, angiogenic, and thrombotic pathways are discussed, together with their translational potential and clinical limitations. By integrating immunological, vascular, hematological, and cardiovascular perspectives, this review provides a comprehensive framework for understanding the pathophysiology of pre\u2010eclampsia and identifies important knowledge gaps for future investigation.<\/jats:p>","DOI":"10.1002\/cph4.70209","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:54:18Z","timestamp":1782888858000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Immuno\u2010Cardiovascular Storm of Pre\u2010Eclampsia: Cytokine\u2010Mediated Endothelial Injury, Thrombosis, and Maternal Cardiovascular Instability"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-0161","authenticated-orcid":false,"given":"Emmanuel Ifeanyi","family":"Obeagu","sequence":"first","affiliation":[{"name":"Division of Haematology, Department of Biomedical and Laboratory Science Africa University  Mutare Zimbabwe"},{"name":"Department of Molecular Medicine and Haematology, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhh.2011.29"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/0300\u20101652.128180"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17101691"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c200008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1144170"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0020\u20107292(98)00138\u20106"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l2381"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15566"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2024.1419731"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.02.042"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2023.10.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100036\u20101592294"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.653228"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/367284"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2021.01.004"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3522"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179545X17752325"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000004190"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010022\u201000670\u20100"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.5830\/CVJA\u20102016\u2010009"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2022.2080557"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.6.10.1367"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161023905"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.71"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150702"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a023473"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmae007"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.637703"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4103\/2277\u20109175.218032"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236008"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12742"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9121756"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci13030154"},{"issue":"2","key":"e_1_2_7_35_1","first-page":"105","article-title":"The Role of Immune Activation in Contributing to Vascular Dysfunction and the Pathophysiology of Hypertension During Preeclampsia","volume":"62","author":"Lamarca B.","year":"2010","journal-title":"Minerva Ginecologica"},{"issue":"4","key":"e_1_2_7_36_1","first-page":"309","article-title":"Endothelial Dysfunction. An Important Mediator in the Pathophysiology of Hypertension During Pre\u2010Eclampsia","volume":"64","author":"Lamarca B.","year":"2012","journal-title":"Minerva Ginecologica"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906\u2010016\u20100633\u2010x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.930582"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1112603"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1456171"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs\u20104121735\/v1"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02630"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)64127\u20102"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20100528.1994.tb13146.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.01.359"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2025.101054"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17189"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6268276"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.021"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003664"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3864941"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00070\u20107"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14217516"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000030870"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11247436"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12155039"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010020\u201008804\u20107"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.4314\/ahs.v19i2.4"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.4314\/ahs.v18i3.15"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14093121"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1530\/VB\u201025\u20100009"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1285898"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12071715"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010019\u20100119\u20106"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2025.100279"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02597"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2016.04.008"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.853127"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354200"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313276"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1111726"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1111371"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9259646"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.11.561"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2008.11.009"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2014.02.006"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689720920830"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0165\u20100378(03)00045\u20107"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00372"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010023\u201005234\u20101"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.71966"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1063\u20104584(03)00156\u20100"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c240003"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.51512"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacadv.2024.100980"},{"issue":"1","key":"e_1_2_7_86_1","first-page":"7","article-title":"Pre\u2010Eclampsia: Is It All in the Placenta?","volume":"16","author":"Singh H. J.","year":"2009","journal-title":"Malaysian Journal of Medical Sciences"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.13722"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667841"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264\u2010016\u20100055\u20104"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01568"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2016.08.008"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070781"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.944104"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102024\u2010091882"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010020\u201000899\u2010z"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.70123"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.2147\/VHRM.S20181"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1429"},{"key":"e_1_2_7_99_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.651"},{"key":"e_1_2_7_100_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612563"},{"key":"e_1_2_7_101_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm15051944"},{"key":"e_1_2_7_102_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.116.003497"},{"key":"e_1_2_7_103_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010132"},{"key":"e_1_2_7_104_1","doi-asserted-by":"publisher","DOI":"10.1177\/10760296221097383"},{"key":"e_1_2_7_105_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1602338"},{"key":"e_1_2_7_106_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010008\u20100733\u20100"},{"key":"e_1_2_7_107_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.910908"}],"container-title":["Comprehensive Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cph4.70209","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cph4.70209","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cph4.70209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:51:06Z","timestamp":1787719866000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cph4.70209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":106,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cph4.70209"],"URL":"https:\/\/doi.org\/10.1002\/cph4.70209","archive":["Portico"],"relation":{},"ISSN":["2040-4603","2040-4603"],"issn-type":[{"value":"2040-4603","type":"print"},{"value":"2040-4603","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"2026-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70209"}}