{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:43:01Z","timestamp":1792460581401,"version":"4.5.0"},"reference-count":111,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR22491\/MED\/97\/361\/2016"],"award-info":[{"award-number":["BT\/PR22491\/MED\/97\/361\/2016"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Early\u2010onset preeclampsia (EOPE) is a severe gestational hypertensive disorder with significant feto\u2010maternal morbidity and mortality due to uteroplacental insufficiency. Circulating extracellular vesicles of placental origin (EV\u2010P) are known to be involved in the pathophysiology of EOPE and might serve as an ideal reservoir for its specific biomarkers. Therefore, we aimed to characterize and perform comparative proteomics of circulating EV\u2010P from healthy pregnant and EOPE women before delivery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>The EV\u2010P from both groups were isolated using immunoaffinity and were characterized using transmission electron microscopy, dynamic light scattering, nanoparticle tracking analysis, and immunoblotting. Following IgG albumin depletion, the pooled proteins that were isolated from EV\u2010P of both groups were subjected to quantitative TMT proteomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Circulating term EV\u2010P isolated from both groups revealed \u223c150\u00a0nm spherical vesicles containing CD9 and CD63 along with placental PLAP and HLA\u2010G proteins. Additionally, the concentration of EOPE\u2010derived EV\u2010P was significantly increased. A total of 208 proteins were identified, with 26 among them being differentially abundant in EV\u2010P of EOPE women. This study linked the pathophysiology of EOPE to 19 known and seven novel proteins associated with innate immune responses such as complement and TLR signaling along with hemostasis and oxygen homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The theory suggesting circulating EVs of placental origin could mimic molecular information from the parent organ\u2014\u201cthe placenta\u201d\u2014is strengthened by this study. The findings pave the way for possible discovery of novel prognostic and predictive biomarkers as well as provide insight into the mechanisms driving the pathogenesis of EOPE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13860","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T11:44:00Z","timestamp":1716896640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Differential proteomics of circulating extracellular vesicles of placental origin isolated from women with early\u2010onset preeclampsia reveal aberrant innate immune and hemostasis processes"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0218-2280","authenticated-orcid":false,"given":"Aishwarya","family":"Rao","sequence":"first","affiliation":[{"name":"Innate Immunity Department ICMR\u2010National Institute for Research in Reproductive and Child Health (ICMR\u2010NIRRCH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rambhadur","family":"Subedi","sequence":"additional","affiliation":[{"name":"Innate Immunity Department ICMR\u2010National Institute for Research in Reproductive and Child Health (ICMR\u2010NIRRCH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra","family":"Kundu","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Centre ICMR\u2010National Institute for Research in Reproductive and Child Health (ICMR\u2010NIRRCH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Idicula\u2010Thomas","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Centre ICMR\u2010National Institute for Research in Reproductive and Child Health (ICMR\u2010NIRRCH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Shinde","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Department ICMR\u2010National Institute for Research in Reproductive and Child Health (ICMR\u2010NIRRCH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Bansal","sequence":"additional","affiliation":[{"name":"Nowrosjee Wadia Maternity Hospital (NWMH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Balsarkar","sequence":"additional","affiliation":[{"name":"Nowrosjee Wadia Maternity Hospital (NWMH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan","family":"Mayadeo","sequence":"additional","affiliation":[{"name":"King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanjit Kumar","family":"Das","sequence":"additional","affiliation":[{"name":"Stem Cell Biology Department ICMR\u2010National Institute for Research in Reproductive and Child Health (ICMR\u2010NIRRCH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafisa","family":"Balasinor","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Department ICMR\u2010National Institute for Research in Reproductive and Child Health (ICMR\u2010NIRRCH)  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taruna","family":"Madan","sequence":"additional","affiliation":[{"name":"Development Research Indian Council of Medical Research V. Ramalingaswami Bhawan  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2013.05.005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002783"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010019\u20100119\u20106"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpm\u20102016\u20100180"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02597"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.717879"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.18203\/2320\u20101770.ijrcog20182333"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.08.019"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404\u2010014\u20103176\u2010x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100032\u20101310527"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a023028"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062120"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.06.004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815\u2010018\u20101343\u2010x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15144"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22083904"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098667"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479\u20105876\u201012\u2010204"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2016.08.078"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020245"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.111.097014"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaa198"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijmr.ijmr_2143_22"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154795"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2020.02.032"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa009"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12377"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201023\u20100215"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12311"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20143457"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301885"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2567"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2007.03.008"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4185"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.166747"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.05.034"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201015\u2010293"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014\u2010022\u201009342\u20104"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430193"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1559\u20100275\u201011\u201040"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014\u2010021\u201009313\u20101"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010021\u201000730\u20101"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa970"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.98.12051147"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108815"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400796200"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925\u20104439(03)00063\u20102"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100897.2006.00435.x"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1586\/eog.10.43"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/6.6.535"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.10.005"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.791535"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12788"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12291\u2010013\u20100408\u2010y"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2000484117"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2007.04.007"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.877344"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859\u2010021\u201004219\u2010z"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1078\/0065-1281-00708"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390\u2010020\u201001177\u20109"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.921997"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029607299986"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2021.100503"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113115"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293\u2010018\u20100195\u20105"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906\u2010020\u20101033\u20109"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14280"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.14744\/AnatolJCardiol.2023.2865"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201082733\u2010z"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.3889\/oamjms.2019.601"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.102723"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001865"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10517\u2010019\u201004383\u20106"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0274398"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.780043"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.56141"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2017.09.004"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073357"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2506"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13570"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2015.00187"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/dsn014"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep36780"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211\u20105463.13085"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26061642"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2273"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1075604"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1060850"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065658"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00955"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2016.07.305"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201700165"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002981"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1177\/2058739219858527"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150702"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1017\/S204017441900014X"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102249.2012.04590.x"},{"key":"e_1_2_8_100_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00312"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.194324"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201086073\u2010w"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102016\u201003\u2010705434"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201023706\u20107"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2012.03.488"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(91)90141-W"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.9.5949"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.11.011"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.10.022"},{"key":"e_1_2_8_110_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17189"},{"key":"e_1_2_8_111_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13208"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.07.012"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13860","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T17:35:33Z","timestamp":1719336933000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.13860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,28]]},"references-count":111,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/aji.13860"],"URL":"https:\/\/doi.org\/10.1111\/aji.13860","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,28]]},"assertion":[{"value":"2024-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13860"}}