Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome
Preeclampsia (PE) is a leading cause of morbidity and mortality during pregnancy. The initiating processes in PE are poorly understood, and the only effective intervention is premature delivery, which threatens the well-being of the child. The Antiphospholipid Syndrome (APS), which is characterized...
Saved in:
| Published in | Circulation research Vol. 129; no. 7; pp. 735 - 750 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Lippincott Williams & Wilkins
17.09.2021
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 0009-7330 1524-4571 1524-4571 |
| DOI | 10.1161/CIRCRESAHA.120.318941 |
Cover
| Abstract | Preeclampsia (PE) is a leading cause of morbidity and mortality during pregnancy. The initiating processes in PE are poorly understood, and the only effective intervention is premature delivery, which threatens the well-being of the child. The Antiphospholipid Syndrome (APS), which is characterized by circulating antiphospholipid antibodies (aPL), is a common risk factor for PE, and also for fetal demise, premature birth and intrauterine growth restriction. This work presents an animal model of APS-related PE, revealing that aPL administration to pregnant mice induces PE and fetal compromise via ApoER2 in trophoblasts. Mechanistically, via ApoER2, aPL activate PP2A, which upregulates MMP14 and HIF1α, the latter via dephosphorylation of PHD2, leading to increased production of soluble endoglin, which is a known driver of PE. A role for PP2A in PE pathogenesis is revealed, and linkage of PP2A to PHD2 and HIF1α is demonstrated in placentas from both APS patients and women with PE from causes other than APS. As importantly, pharmacologic inhibition of PP2A affords full protection from both aPL-induced PE and the fetal complications. Future research should interrogate how PP2A is activated in PE not associated with APS, and how PP2A can be targeted to combat PE. |
|---|---|
| AbstractList | [Figure: see text].[Figure: see text]. Preeclampsia (PE) is a leading cause of morbidity and mortality during pregnancy. The initiating processes in PE are poorly understood, and the only effective intervention is premature delivery, which threatens the well-being of the child. The Antiphospholipid Syndrome (APS), which is characterized by circulating antiphospholipid antibodies (aPL), is a common risk factor for PE, and also for fetal demise, premature birth and intrauterine growth restriction. This work presents an animal model of APS-related PE, revealing that aPL administration to pregnant mice induces PE and fetal compromise via ApoER2 in trophoblasts. Mechanistically, via ApoER2, aPL activate PP2A, which upregulates MMP14 and HIF1α, the latter via dephosphorylation of PHD2, leading to increased production of soluble endoglin, which is a known driver of PE. A role for PP2A in PE pathogenesis is revealed, and linkage of PP2A to PHD2 and HIF1α is demonstrated in placentas from both APS patients and women with PE from causes other than APS. As importantly, pharmacologic inhibition of PP2A affords full protection from both aPL-induced PE and the fetal complications. Future research should interrogate how PP2A is activated in PE not associated with APS, and how PP2A can be targeted to combat PE. [Figure: see text]. |
| Author | Herz, Joachim Natale, David R. Nguyen, An Xu, Lin Shaul, Philip W. Sacharidou, Anastasia Lo, Julie Montalbano, Alina P. Chu, Haiyan Marciano, Denise K. Li, Chun Shen, Yu-Min Hui, David Y. Chambliss, Ken L. Xiao, Xue Natale, Bryony V. Leone, Gustavo W. Abrahams, Vikki M. Salmon, Jane E. Mineo, Chieko |
| AuthorAffiliation | Froedtert-Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee (G.W.L.) Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT (V.M.A.) Internal Medicine (Y.-M.S., D.K.M.), University of Texas Southwestern Medical Center, Dallas Biochemistry and Obstetrics and Gynecology (A.P.M.), University of Texas Southwestern Medical Center, Dallas Molecular Genetics (J.H.), University of Texas Southwestern Medical Center, Dallas Obstetrics and Gynecology (J.L.), University of Texas Southwestern Medical Center, Dallas Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) Medicine, Hospital for Special Surgery, Weill Cornell Medical College, New York (J.E.S.) Population and Data Sciences and Pediatrics (X.X., L.X.), University of Texas Southwestern Medical Center, Dallas Pathology, University of Cincinnati College of Medicine (D.Y.H.) |
| AuthorAffiliation_xml | – name: Obstetrics and Gynecology (J.L.), University of Texas Southwestern Medical Center, Dallas – name: Internal Medicine (Y.-M.S., D.K.M.), University of Texas Southwestern Medical Center, Dallas – name: Froedtert-Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee (G.W.L.) – name: Pathology, University of Cincinnati College of Medicine (D.Y.H.) – name: Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT (V.M.A.) – name: Population and Data Sciences and Pediatrics (X.X., L.X.), University of Texas Southwestern Medical Center, Dallas – name: Molecular Genetics (J.H.), University of Texas Southwestern Medical Center, Dallas – name: Biochemistry and Obstetrics and Gynecology (A.P.M.), University of Texas Southwestern Medical Center, Dallas – name: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) – name: Medicine, Hospital for Special Surgery, Weill Cornell Medical College, New York (J.E.S.) – name: 5 Froedtert-Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA – name: 12 Biochemistry and Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas – name: 11 Obstetrics and Gynaecology, School of Medicine, Queen’s University, Ontario, Canada – name: 7 Pathology, University of Cincinnati College of Medicine, Cincinnati – name: 10 Obstetrics, Gynecology & Reproductive Science, University of California San Diego, La Jolla, CA 92093, USA – name: 6 Molecular Genetics, University of Texas Southwestern Medical Center, Dallas – name: 9 Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510 USA – name: 8 Cell Biology, University of Texas Southwestern Medical Center, Dallas – name: 3 Internal Medicine, University of Texas Southwestern Medical Center, Dallas – name: 4 Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas – name: 13 Population and Data Sciences and Pediatrics, University of Texas Southwestern Medical Center – name: 2 Medicine, Hospital for Special Surgery, Weill Cornell Medical College, New York – name: 1 Center for Pulmonary and Vascular Biology, Pediatrics, University of Texas Southwestern Medical Center, Dallas |
| Author_xml | – sequence: 1 givenname: Haiyan surname: Chu fullname: Chu, Haiyan organization: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) – sequence: 2 givenname: Anastasia surname: Sacharidou fullname: Sacharidou, Anastasia organization: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) – sequence: 3 givenname: An surname: Nguyen fullname: Nguyen, An organization: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) – sequence: 4 givenname: Chun surname: Li fullname: Li, Chun organization: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) – sequence: 5 givenname: Ken L. surname: Chambliss fullname: Chambliss, Ken L. organization: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) – sequence: 6 givenname: Jane E. surname: Salmon fullname: Salmon, Jane E. organization: Medicine, Hospital for Special Surgery, Weill Cornell Medical College, New York (J.E.S.) – sequence: 7 givenname: Yu-Min surname: Shen fullname: Shen, Yu-Min organization: Internal Medicine (Y.-M.S., D.K.M.), University of Texas Southwestern Medical Center, Dallas – sequence: 8 givenname: Julie surname: Lo fullname: Lo, Julie organization: Obstetrics and Gynecology (J.L.), University of Texas Southwestern Medical Center, Dallas – sequence: 9 givenname: Gustavo W. surname: Leone fullname: Leone, Gustavo W. organization: Froedtert-Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee (G.W.L.) – sequence: 10 givenname: Joachim surname: Herz fullname: Herz, Joachim organization: Molecular Genetics (J.H.), University of Texas Southwestern Medical Center, Dallas – sequence: 11 givenname: David Y. surname: Hui fullname: Hui, David Y. organization: Pathology, University of Cincinnati College of Medicine (D.Y.H.) – sequence: 12 givenname: Denise K. surname: Marciano fullname: Marciano, Denise K. organization: Internal Medicine (Y.-M.S., D.K.M.), University of Texas Southwestern Medical Center, Dallas – sequence: 13 givenname: Vikki M. surname: Abrahams fullname: Abrahams, Vikki M. organization: Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT (V.M.A.) – sequence: 14 givenname: Bryony V. surname: Natale fullname: Natale, Bryony V. organization: Obstetrics, Gynecology & Reproductive Science, University of California San Diego, La Jolla (B.V.N., D.R.N.) – sequence: 15 givenname: Alina P. surname: Montalbano fullname: Montalbano, Alina P. organization: Biochemistry and Obstetrics and Gynecology (A.P.M.), University of Texas Southwestern Medical Center, Dallas – sequence: 16 givenname: Xue surname: Xiao fullname: Xiao, Xue organization: Population and Data Sciences and Pediatrics (X.X., L.X.), University of Texas Southwestern Medical Center, Dallas – sequence: 17 givenname: Lin surname: Xu fullname: Xu, Lin organization: Population and Data Sciences and Pediatrics (X.X., L.X.), University of Texas Southwestern Medical Center, Dallas – sequence: 18 givenname: David R. surname: Natale fullname: Natale, David R. organization: Obstetrics, Gynecology & Reproductive Science, University of California San Diego, La Jolla (B.V.N., D.R.N.) – sequence: 19 givenname: Philip W. surname: Shaul fullname: Shaul, Philip W. organization: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) – sequence: 20 givenname: Chieko surname: Mineo fullname: Mineo, Chieko organization: Center for Pulmonary and Vascular Biology, Pediatrics (H.C., A.S., A.N., C.L., K.L.C., P.W.S., C.M.) |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34404233$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFUstuEzEUtVARTQOfAPKSzaR-zUtISKMQaKVWRGlhazkzdxiDM57ankTZ8uV1m0IpLFhZss_D95x7go562wNCrymZUZrR0_n5ar5aXFVn1YwyMuO0KAV9hiY0ZSIRaU6P0IQQUiY55-QYnXj_nRAqOCtfoGMuBBGM8wn6uXQ2gO7xsrN-6FRQHjCrcFUHvVVB2x5_1QpXg12sGI64a2eHzq6N8sHjD05vweOlA6iN2gw-QiNG4Us7Rp1L24DBtsWhA1z1QQ_3JtboQTf4at83zm7gJXreKuPh1cM5RV8-Lq7nZ8nF50_n8-oiqUWa5UlZlDwjJS0zyKlKs7osmjTP25zxlK15KzLOsoIAE23B1gpU2whIqWCKCQFA-RRlB92xH9R-p4yRg9Mb5faSEnkXqqy1qx141SkZQ5WHUCPx_YE4jOsNNDX0walHslVaPn3pdSe_2a0shCjKmP8UvX0QcPZmBB_kRvsajFE9xKAkSzOW0pLlRYS--dPrt8mvxiIgPQBqZ7130P4zxONmPB3i3V-8Wof7guOXtfkvWxzYO2sCOP_DjDtwsgNlQifjnhFOKEsYYTRWlJPk7irnt52Nzwg |
| CitedBy_id | crossref_primary_10_1016_j_clim_2023_109745 crossref_primary_10_3389_fphys_2021_764702 crossref_primary_10_1080_10408363_2024_2305121 crossref_primary_10_1093_rheumatology_kead537 crossref_primary_10_1136_bmj_2021_069717 crossref_primary_10_1161_CIRCRESAHA_122_320395 crossref_primary_10_1186_s12951_023_02179_5 crossref_primary_10_1016_j_jri_2024_104389 crossref_primary_10_3390_physiologia2030007 crossref_primary_10_1038_s41598_024_82451_2 crossref_primary_10_3390_biomedicines11102681 crossref_primary_10_3390_cells12162096 |
| Cites_doi | 10.1038/s41598-018-35606-x 10.1172/JCI83918 10.1016/j.placenta.2005.09.007 10.1038/77076 10.1523/JNEUROSCI.4566-05.2006 10.2353/ajpath.2010.090800 10.1002/dvg.20276 10.1161/HYPERTENSIONAHA.115.05024 10.1146/annurev.cellbio.19.111401.091942 10.22237/jmasm/1462075500 10.1038/nrdp.2017.103 10.1177/0961203318787035 10.2353/ajpath.2008.070640 10.1016/j.cell.2006.11.033 10.1158/1078-0432.CCR-07-0793 10.1056/NEJMoa031884 10.1530/rep.1.00234 10.1126/science.1325671 10.1016/j.cell.2008.02.041 10.1002/acr.22066 10.1016/s0898-6568(00)00123-6 10.1136/annrheumdis-2013-204838 10.1056/NEJMra002974 10.1016/0006-2952(93)90109-a 10.1182/blood-2017-11-814681 10.1128/MCB.25.7.2733-2743.2005 10.1371/journal.pone.0158757 10.1038/nrrheum.2011.52 10.1016/j.jesp.2010.02.007 10.1161/CIRCULATIONAHA.112.101261 10.1016/j.ajpath.2011.11.014 10.1182/blood-2012-03-378646 10.1161/CIRCULATIONAHA.119.043490 10.1093/humrep/den178 10.1097/01.AOG.0000437382.03963.88 10.1152/physiolgenomics.00125.2015 10.1158/0008-5472.CAN-09-4466 10.1016/j.celrep.2017.01.051 10.1161/CIRCRESAHA.118.313276 10.1016/j.lfs.2017.10.006 10.1136/bmj.i1753 10.1016/j.ydbio.2016.12.013 10.1002/tox.22273 10.1038/nm1429 10.1016/j.placenta.2017.06.343 10.1016/j.placenta.2004.02.011 10.1172/JCI89333 10.1056/NEJMra1112830 10.1172/JCI17189 10.1093/humrep/17.4.1067 10.1111/j.1742-4658.2012.08579.x 10.1007/s11936-018-0653-8 10.1002/art.39453 10.1177/0961203315572714 10.1242/dev.020099 10.1021/pr300694b 10.1002/(SICI)1097-0177(199904)214:4<303::AID-AJA3>3.0.CO;2-B 10.1161/HYPERTENSIONAHA.114.04670 10.1161/HYPERTENSIONAHA.117.09246 10.1016/S0140-6736(10)60709-X 10.1016/j.tibs.2007.12.004 10.1038/s41598-019-39426-5 10.1146/annurev.med.59.110106.214058 10.1016/j.placenta.2009.08.007 10.1038/nmeth1019 10.1016/S0021-9258(17)37144-2 10.1016/S0140-6736(10)60518-1 10.1177/0961203308096344 10.1074/jbc.M207160200 10.1093/emboj/19.21.5682 10.1097/AOG.0b013e3181a45b25 10.1006/dbio.1994.1223 10.1111/j.1349-7006.2010.01523.x 10.1371/journal.pone.0039864 10.1016/j.autrev.2014.02.003 10.1007/1-84628-009-5_29 10.1038/s41598-017-06008-2 10.3389/fimmu.2015.00205 10.1371/journal.pone.0012418 |
| ContentType | Journal Article |
| Copyright | Lippincott Williams & Wilkins |
| Copyright_xml | – notice: Lippincott Williams & Wilkins |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM ADTOC UNPAY |
| DOI | 10.1161/CIRCRESAHA.120.318941 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) Unpaywall for CDI: Periodical Content Unpaywall |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 3 dbid: UNPAY name: Unpaywall url: https://proxy.k.utb.cz/login?url=https://unpaywall.org/ sourceTypes: Open Access Repository |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1524-4571 |
| EndPage | 750 |
| ExternalDocumentID | 10.1161/circresaha.120.318941 PMC8448973 34404233 10_1161_CIRCRESAHA_120_318941 00003012-202109170-00007 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NICHD NIH HHS grantid: R01 HD100179 – fundername: NINDS NIH HHS grantid: R01 NS093382 – fundername: NIA NIH HHS grantid: RF1 AG053391 – fundername: NHLBI NIH HHS grantid: R01 HL109604 – fundername: NHLBI NIH HHS grantid: R37 HL063762 – fundername: NHLBI NIH HHS grantid: R01 HL144969 – fundername: CIHR grantid: 201203MOP-275374-CIA-CBBA-109624 – fundername: NHLBI NIH HHS grantid: T32 HL098040 – fundername: NICHD NIH HHS grantid: R01 HD094395 – fundername: NHLBI NIH HHS grantid: R01 HL147403 |
| GroupedDBID | --- -~X .-D .3C .Z2 01R 0R~ 18M 1J1 29B 2WC 40H 4Q1 4Q2 4Q3 53G 5GY 5RE 5VS 71W 77Y 7O~ AAAAV AAAXR AAGIX AAHPQ AAIQE AAMOA AAMTA AAQKA AARTV AASCR AASOK AAXQO ABASU ABBUW ABDIG ABJNI ABOCM ABPXF ABQRW ABVCZ ABXVJ ABZAD ABZZY ACDDN ACEWG ACGFO ACGFS ACILI ACLDA ACNWC ACPRK ACWDW ACWRI ACXJB ACXNZ ACZKN ADBBV ADGGA ADHPY AE3 AE6 AENEX AFBFQ AFDTB AFUWQ AGINI AHMBA AHOMT AHQNM AHVBC AIJEX AINUH AJCLO AJIOK AJNWD AJZMW AKCTQ AKULP ALKUP ALMA_UNASSIGNED_HOLDINGS ALMTX AMJPA AMKUR AMNEI AOHHW AOQMC BAWUL BOYCO BQLVK C45 CS3 DIK DIWNM DU5 E.X E3Z EBS EEVPB EJD ERAAH EX3 F2K F2L F2M F2N F5P FCALG FL- FRP GNXGY GQDEL GX1 H0~ HLJTE HZ~ IKREB IKYAY IN~ IPNFZ JK3 JK8 K8S KD2 KMI KQ8 L-C L7B N9A N~7 N~B O9- OAG OAH OB2 OK1 OL1 OLG OLH OLU OLV OLY OLZ OPUJH OVD OVDNE OVIDH OVLEI OWW OWY OXXIT P2P PQQKQ RAH RIG RLZ S4R S4S T8P TEORI TR2 TSPGW UPT V2I VVN W3M W8F WH7 WOQ WOW X3V X3W YFH YOC ZFV AAYXX ADKSD ADSXY CITATION ACIJW AWKKM CGR CUY CVF ECM EIF NPM ODA OLW RHF 7X8 5PM .55 .GJ 1CY 41~ ACCJW ADFPA ADGHP ADNKB ADTOC AEETU AFFNX AHRYX AJNYG BS7 BYPQX C1A DUNZO FW0 H13 H~9 J5H JF9 JG8 MVM N~M OCUKA ORVUJ OUVQU OWU OWV OWX OWZ P-K R58 UNPAY X7M XXN XYM ZGI ZZMQN |
| ID | FETCH-LOGICAL-c4567-9893609196e71a56c98d577f72352b3f4632680e24f82baeafd4e5142a244ee13 |
| IEDL.DBID | UNPAY |
| ISSN | 0009-7330 1524-4571 |
| IngestDate | Wed Oct 01 15:40:44 EDT 2025 Tue Sep 30 17:19:26 EDT 2025 Mon Sep 08 07:11:59 EDT 2025 Wed Feb 19 02:27:11 EST 2025 Thu Apr 24 23:04:17 EDT 2025 Wed Oct 01 04:48:54 EDT 2025 Fri May 16 03:50:45 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 7 |
| Keywords | antiphospholipid syndrome placenta endoglin preeclampsia proteinuria trophoblasts |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c4567-9893609196e71a56c98d577f72352b3f4632680e24f82baeafd4e5142a244ee13 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 H.C. and A.S. designed the experiments, performed the experiments, and analyzed the data. A.N., C.L and B.V.N. performed the experiments and analyzed the data. K.L.C., J.H., G.W.L. and D.Y.H. generated the genetically modified mouse strains and performed their initial characterization. J.E.S. and Y-M.S. recruited the individuals who provided the human IgG-based reagents. J.L. and A.P.M. provided human placentas from APS or PE patients. V.M.A. provided the human trophoblast strain and aided in experimental design. D.K.M. aided in experimental designs related to proteinuria and kidney functions. L.X. and X.X. performed the statistical analyses. D.R.N., P.W.S. and C.M. designed the experiments, analyzed the data and wrote the manuscript. All authors provided feedback on the manuscript. AUTHOR CONTRIBUTIONS Co-first authors Co-senior authors. |
| ORCID | 0000-0002-1901-1717 0000-0002-9098-0617 0000-0001-8365-455X 0000-0003-1157-4002 0000-0001-7333-2151 0000-0002-4978-6177 0000-0001-6119-816X 0000-0002-8506-3400 |
| OpenAccessLink | https://proxy.k.utb.cz/login?url=https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.120.318941 |
| PMID | 34404233 |
| PQID | 2562519278 |
| PQPubID | 23479 |
| PageCount | 16 |
| ParticipantIDs | unpaywall_primary_10_1161_circresaha_120_318941 pubmedcentral_primary_oai_pubmedcentral_nih_gov_8448973 proquest_miscellaneous_2562519278 pubmed_primary_34404233 crossref_primary_10_1161_CIRCRESAHA_120_318941 crossref_citationtrail_10_1161_CIRCRESAHA_120_318941 wolterskluwer_health_00003012-202109170-00007 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2021-September-17 |
| PublicationDateYYYYMMDD | 2021-09-17 |
| PublicationDate_xml | – month: 09 year: 2021 text: 2021-September-17 day: 17 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Circulation research |
| PublicationTitleAlternate | Circ Res |
| PublicationYear | 2021 |
| Publisher | Lippincott Williams & Wilkins |
| Publisher_xml | – name: Lippincott Williams & Wilkins |
| References | Wobbrock JO (e_1_3_6_34_2) e_1_3_6_30_2 e_1_3_6_51_2 e_1_3_6_76_2 e_1_3_6_32_2 e_1_3_6_53_2 e_1_3_6_74_2 e_1_3_6_72_2 e_1_3_6_70_2 e_1_3_6_13_2 e_1_3_6_38_2 e_1_3_6_59_2 e_1_3_6_11_2 e_1_3_6_17_2 e_1_3_6_55_2 e_1_3_6_15_2 e_1_3_6_36_2 e_1_3_6_57_2 e_1_3_6_78_2 e_1_3_6_40_2 e_1_3_6_65_2 e_1_3_6_21_2 e_1_3_6_42_2 e_1_3_6_63_2 e_1_3_6_61_2 e_1_3_6_80_2 e_1_3_6_4_2 Parke AL (e_1_3_6_19_2) 2006 e_1_3_6_2_2 e_1_3_6_8_2 e_1_3_6_6_2 e_1_3_6_27_2 e_1_3_6_48_2 e_1_3_6_29_2 e_1_3_6_23_2 e_1_3_6_44_2 e_1_3_6_69_2 e_1_3_6_25_2 e_1_3_6_46_2 e_1_3_6_67_2 e_1_3_6_52_2 e_1_3_6_75_2 e_1_3_6_31_2 e_1_3_6_54_2 e_1_3_6_73_2 e_1_3_6_10_2 e_1_3_6_71_2 e_1_3_6_50_2 e_1_3_6_14_2 e_1_3_6_37_2 e_1_3_6_12_2 e_1_3_6_39_2 e_1_3_6_18_2 e_1_3_6_33_2 e_1_3_6_56_2 e_1_3_6_79_2 e_1_3_6_16_2 e_1_3_6_35_2 e_1_3_6_58_2 e_1_3_6_77_2 e_1_3_6_41_2 e_1_3_6_64_2 e_1_3_6_20_2 e_1_3_6_43_2 e_1_3_6_62_2 e_1_3_6_60_2 e_1_3_6_81_2 e_1_3_6_5_2 e_1_3_6_3_2 e_1_3_6_9_2 e_1_3_6_7_2 e_1_3_6_26_2 e_1_3_6_49_2 e_1_3_6_28_2 e_1_3_6_22_2 e_1_3_6_45_2 e_1_3_6_68_2 e_1_3_6_24_2 e_1_3_6_47_2 e_1_3_6_66_2 |
| References_xml | – ident: e_1_3_6_75_2 doi: 10.1038/s41598-018-35606-x – ident: e_1_3_6_53_2 doi: 10.1172/JCI83918 – ident: e_1_3_6_37_2 doi: 10.1016/j.placenta.2005.09.007 – ident: e_1_3_6_78_2 doi: 10.1038/77076 – ident: e_1_3_6_49_2 doi: 10.1523/JNEUROSCI.4566-05.2006 – ident: e_1_3_6_64_2 doi: 10.2353/ajpath.2010.090800 – ident: e_1_3_6_27_2 doi: 10.1002/dvg.20276 – ident: e_1_3_6_52_2 doi: 10.1161/HYPERTENSIONAHA.115.05024 – ident: e_1_3_6_51_2 doi: 10.1146/annurev.cellbio.19.111401.091942 – ident: e_1_3_6_33_2 doi: 10.22237/jmasm/1462075500 – ident: e_1_3_6_21_2 doi: 10.1038/nrdp.2017.103 – ident: e_1_3_6_16_2 doi: 10.1177/0961203318787035 – ident: e_1_3_6_67_2 doi: 10.2353/ajpath.2008.070640 – ident: e_1_3_6_44_2 doi: 10.1016/j.cell.2006.11.033 – ident: e_1_3_6_73_2 doi: 10.1158/1078-0432.CCR-07-0793 – ident: e_1_3_6_71_2 doi: 10.1056/NEJMoa031884 – ident: e_1_3_6_42_2 doi: 10.1530/rep.1.00234 – ident: e_1_3_6_45_2 doi: 10.1126/science.1325671 – ident: e_1_3_6_48_2 doi: 10.1016/j.cell.2008.02.041 – ident: e_1_3_6_36_2 doi: 10.1002/acr.22066 – start-page: 143 volume-title: 29th Annual Chi Conference on Human Factors in Computing Systems ident: e_1_3_6_34_2 – ident: e_1_3_6_39_2 doi: 10.1016/s0898-6568(00)00123-6 – ident: e_1_3_6_12_2 doi: 10.1136/annrheumdis-2013-204838 – ident: e_1_3_6_15_2 doi: 10.1056/NEJMra002974 – ident: e_1_3_6_62_2 doi: 10.1016/0006-2952(93)90109-a – ident: e_1_3_6_25_2 doi: 10.1182/blood-2017-11-814681 – ident: e_1_3_6_50_2 doi: 10.1128/MCB.25.7.2733-2743.2005 – ident: e_1_3_6_24_2 doi: 10.1371/journal.pone.0158757 – ident: e_1_3_6_22_2 doi: 10.1038/nrrheum.2011.52 – ident: e_1_3_6_35_2 doi: 10.1016/j.jesp.2010.02.007 – ident: e_1_3_6_56_2 doi: 10.1161/CIRCULATIONAHA.112.101261 – ident: e_1_3_6_59_2 doi: 10.1016/j.ajpath.2011.11.014 – ident: e_1_3_6_20_2 doi: 10.1182/blood-2012-03-378646 – ident: e_1_3_6_28_2 doi: 10.1161/CIRCULATIONAHA.119.043490 – ident: e_1_3_6_41_2 doi: 10.1093/humrep/den178 – ident: e_1_3_6_2_2 doi: 10.1097/01.AOG.0000437382.03963.88 – ident: e_1_3_6_7_2 doi: 10.1152/physiolgenomics.00125.2015 – ident: e_1_3_6_57_2 doi: 10.1158/0008-5472.CAN-09-4466 – ident: e_1_3_6_68_2 doi: 10.1016/j.celrep.2017.01.051 – ident: e_1_3_6_8_2 doi: 10.1161/CIRCRESAHA.118.313276 – ident: e_1_3_6_69_2 doi: 10.1016/j.lfs.2017.10.006 – ident: e_1_3_6_9_2 doi: 10.1136/bmj.i1753 – ident: e_1_3_6_81_2 doi: 10.1016/j.ydbio.2016.12.013 – ident: e_1_3_6_60_2 doi: 10.1002/tox.22273 – ident: e_1_3_6_55_2 doi: 10.1038/nm1429 – ident: e_1_3_6_76_2 doi: 10.1016/j.placenta.2017.06.343 – ident: e_1_3_6_63_2 doi: 10.1016/j.placenta.2004.02.011 – ident: e_1_3_6_74_2 doi: 10.1172/JCI89333 – ident: e_1_3_6_10_2 doi: 10.1056/NEJMra1112830 – ident: e_1_3_6_54_2 doi: 10.1172/JCI17189 – ident: e_1_3_6_18_2 doi: 10.1093/humrep/17.4.1067 – ident: e_1_3_6_43_2 doi: 10.1111/j.1742-4658.2012.08579.x – ident: e_1_3_6_5_2 doi: 10.1007/s11936-018-0653-8 – ident: e_1_3_6_26_2 doi: 10.1002/art.39453 – ident: e_1_3_6_17_2 doi: 10.1177/0961203315572714 – ident: e_1_3_6_80_2 doi: 10.1242/dev.020099 – ident: e_1_3_6_31_2 doi: 10.1021/pr300694b – ident: e_1_3_6_79_2 doi: 10.1002/(SICI)1097-0177(199904)214:4<303::AID-AJA3>3.0.CO;2-B – ident: e_1_3_6_29_2 doi: 10.1161/HYPERTENSIONAHA.114.04670 – ident: e_1_3_6_6_2 doi: 10.1161/HYPERTENSIONAHA.117.09246 – ident: e_1_3_6_11_2 doi: 10.1016/S0140-6736(10)60709-X – ident: e_1_3_6_38_2 doi: 10.1016/j.tibs.2007.12.004 – ident: e_1_3_6_65_2 doi: 10.1038/s41598-019-39426-5 – ident: e_1_3_6_70_2 doi: 10.1146/annurev.med.59.110106.214058 – ident: e_1_3_6_30_2 doi: 10.1016/j.placenta.2009.08.007 – ident: e_1_3_6_32_2 doi: 10.1038/nmeth1019 – ident: e_1_3_6_46_2 doi: 10.1016/S0021-9258(17)37144-2 – ident: e_1_3_6_3_2 doi: 10.1016/S0140-6736(10)60518-1 – ident: e_1_3_6_23_2 doi: 10.1177/0961203308096344 – ident: e_1_3_6_66_2 doi: 10.1074/jbc.M207160200 – ident: e_1_3_6_47_2 doi: 10.1093/emboj/19.21.5682 – ident: e_1_3_6_4_2 doi: 10.1097/AOG.0b013e3181a45b25 – ident: e_1_3_6_40_2 doi: 10.1006/dbio.1994.1223 – ident: e_1_3_6_61_2 doi: 10.1111/j.1349-7006.2010.01523.x – ident: e_1_3_6_58_2 doi: 10.1371/journal.pone.0039864 – ident: e_1_3_6_13_2 doi: 10.1016/j.autrev.2014.02.003 – start-page: 362 volume-title: In: Hughes’ Syndrome year: 2006 ident: e_1_3_6_19_2 doi: 10.1007/1-84628-009-5_29 – ident: e_1_3_6_77_2 doi: 10.1038/s41598-017-06008-2 – ident: e_1_3_6_14_2 doi: 10.3389/fimmu.2015.00205 – ident: e_1_3_6_72_2 doi: 10.1371/journal.pone.0012418 |
| SSID | ssj0014329 |
| Score | 2.4570098 |
| Snippet | [Figure: see text]. [Figure: see text].[Figure: see text]. Preeclampsia (PE) is a leading cause of morbidity and mortality during pregnancy. The initiating processes in PE are poorly understood, and the only effective... |
| SourceID | unpaywall pubmedcentral proquest pubmed crossref wolterskluwer |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 735 |
| SubjectTerms | Adaptor Proteins, Signal Transducing - metabolism Animals Antibodies, Antiphospholipid - blood Antiphospholipid Syndrome - complications Antiphospholipid Syndrome - metabolism Apoptosis Regulatory Proteins - metabolism Cell Line Female Humans Hypoxia-Inducible Factor 1, alpha Subunit - metabolism LDL-Receptor Related Proteins - metabolism Mice Mice, Inbred C57BL Pre-Eclampsia - etiology Pre-Eclampsia - metabolism Pregnancy Protein Phosphatase 2 - metabolism Trophoblasts - metabolism |
| Title | Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome |
| URI | https://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00003012-202109170-00007 https://www.ncbi.nlm.nih.gov/pubmed/34404233 https://www.proquest.com/docview/2562519278 https://pubmed.ncbi.nlm.nih.gov/PMC8448973 https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.120.318941 |
| UnpaywallVersion | publishedVersion |
| Volume | 129 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVAFT databaseName: Open Access Digital Library customDbUrl: eissn: 1524-4571 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0014329 issn: 1524-4571 databaseCode: KQ8 dateStart: 19530101 isFulltext: true titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html providerName: Colorado Alliance of Research Libraries – providerCode: PRVBFR databaseName: Free Medical Journals customDbUrl: eissn: 1524-4571 dateEnd: 20241003 omitProxy: true ssIdentifier: ssj0014329 issn: 1524-4571 databaseCode: DIK dateStart: 19530101 isFulltext: true titleUrlDefault: http://www.freemedicaljournals.com providerName: Flying Publisher – providerCode: PRVFQY databaseName: GFMER Free Medical Journals customDbUrl: eissn: 1524-4571 dateEnd: 20241003 omitProxy: true ssIdentifier: ssj0014329 issn: 1524-4571 databaseCode: GX1 dateStart: 19530101 isFulltext: true titleUrlDefault: http://www.gfmer.ch/Medical_journals/Free_medical.php providerName: Geneva Foundation for Medical Education and Research |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3da9swEBcjhW0wuu8t-yga7NVpLMmW_WiylnQjJXTN2J6MLMvYNNjGdijd4_7y3fkjbZaHMfZmyOmkXE7W73Kn3xHykUmpYs615XORWCJRnuVx7QKQk9JxkDK8vRS2OHfnK_H5uzNUE9Z9WaVKVW_Ius3l4-Yu46Tb4K59PDu7mMHygjn-k4dRp-fj1fUDF3NMI3KwOl8GP4YOapK3_UbgmBKWcKTd3-JBPTqrAJnVMN0dPbvn0x7o3K-dfLDJS3Vzrdbw_Oi6wBx3fdWWuN85qE4fk2j4il19ytVk00QT_fMP9sf_ssETctjDWBp0fveU3DP5M3J_0Sfqn5NfS-R_yHK6TIu6TFUDhyVlAQ300E6NfssUDcri5IJRkLusijItIsDyTU0_VUiGS5eVMRo8tqxBFGQUXRQb0IP929a0SCiAVxrkTVa2kxTrrMxi-rXnYHhBVqcnl7O51bd7sDSgOGn5AJ1cgC--a6StHFf7XuxImUgGIDHiiXABanpTw0TisUgZlcTCAN5jCiCKMTZ_SUZ5kZvXhBrGE5trP4LXuZBm6kcg4gghFRgKHsdEDD9yqHsudGzJsQ7bmMi1w1v7hmDfsLPvmEy2w8qODORvAz4MHhTCtsVcjMoNmCpkGHgCupbemLzqPGqrkiNnI-N8TOSOr20FkBJ895M8S1tqcA-ibV_CyOOtV-6t9Nbtd1Zq7fhu2F3DxdoEDJoZvE0ZcsjKlodgKt_88wxvyUPUgbU2tnxHRk21Me8B0DXREYQyZ1-O-o37G8gVQsc |
| linkProvider | Unpaywall |
| linkToUnpaywall | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Li9swEBYlC22h9L1t-kKFXp2NJdmyjybdJS1kCdtNaU9GlmVsNtjGdljaY395Z_zIrptDKb0ZMhopk5H1TWb0DSEfmJQq5lxbPheJJRLlWR7XLgA5KR0HKcPbS2Grc3e5EZ-_OUM1Yd2XVapU9Yas21w-bu4yTroN7toni08XC1hesMR_8jDq9Hy8un7kYo5pQo425-vg-9BBTfK23wgcU8ISjrT7WzyoR2cVILMaprulZ3w-HYDOw9rJe7u8VD-u1RaeH1wXmOOur9oS91sH1dkjEg1fsatPuZrtmmimf_7B_vhfNnhMHvYwlgad3z0hd0z-lNxd9Yn6Z-TXGvkfspyu06IuU9XAYUlZQAM9tFOjXzNFg7I4vWAU5C6rokyLCLB8U9OPFZLh0nVljAaPLWsQBRlFV8UO9GD_ti0tEgrglQZ5k5XtJMU2K7OYfuk5GJ6Tzdnp5WJp9e0eLA0oTlo-QCcX4IvvGmkrx9W-FztSJpIBSIx4IlyAmt7cMJF4LFJGJbEwgPeYAohijM2PySQvcvOSUMN4YnPtR_A6F9LM_QhEHCGkAkPB45SI4UcOdc-Fji05tmEbE7l2eGPfEOwbdvadktl-WNmRgfxtwPvBg0LYtpiLUbkBU4UMA09A19KbkhedR-1VcuRsZJxPiRz52l4AKcHHn-RZ2lKDexBt-xJGnuy98mClN24_Wqk18t2wu4aLtQkYNDN4mzLkkJUtD8FcvvrnGV6T-6gDa21s-YZMmmpn3gKga6J3_Zb9DT0hQc4 |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Protein+Phosphatase+2A+Activation+via+ApoER2+in+Trophoblasts+Drives+Preeclampsia+in+a+Mouse+Model+of+the+Antiphospholipid+Syndrome&rft.jtitle=Circulation+research&rft.au=Chu%2C+Haiyan&rft.au=Sacharidou%2C+Anastasia&rft.au=Nguyen%2C+An&rft.au=Li%2C+Chun&rft.date=2021-09-17&rft.issn=0009-7330&rft.eissn=1524-4571&rft.volume=129&rft.issue=7&rft.spage=735&rft.epage=750&rft_id=info:doi/10.1161%2FCIRCRESAHA.120.318941&rft_id=info%3Apmid%2F34404233&rft.externalDocID=PMC8448973 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0009-7330&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0009-7330&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0009-7330&client=summon |