Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice
Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring...
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| creator | Szalai, Gabor Romero, Roberto Chaiworapongsa, Tinnakorn Xu, Yi Wang, Bing Ahn, Hyunyoung Xu, Zhonghui Chiang, Po Jen Sundell, Birgitta Wang, Rona Jiang, Yang Plazyo, Olesya Olive, Mary Tarca, Adi L Dong, Zhong Qureshi, Faisal Papp, Zoltan Hassan, Sonia S Hernandez-Andrade, Edgar Than, Nandor Gabor |
| description | Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.
Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.
Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).
A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway o |
| doi_str_mv | 10.1371/journal.pone.0119547 |
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Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.
Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).
A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119547</identifier><identifier>PMID: 25860260</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviruses ; Age ; Albumin ; Amino Acid Sequence ; Angiogenesis ; Animal models ; Animals ; Aorta ; Blood ; Blood Pressure ; Blood Pressure Monitors ; Carotid artery ; Catheters ; Cell adhesion & migration ; Cesarean section ; Childrens health ; Creatinine ; Disease Models, Animal ; Female ; Fetuses ; Fluorescence ; Gene Expression Profiling ; Gestational Age ; Green fluorescent protein ; Green Fluorescent Proteins - genetics ; Gynecology ; Humans ; Hypertension ; Liver ; Liver diseases ; Medical research ; Medicine ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Monitoring ; Obstetrics ; Pathology ; Phenotype ; Placenta ; Placenta - diagnostic imaging ; Placenta - pathology ; Placenta - physiopathology ; Postpartum ; Pre-eclampsia ; Pre-Eclampsia - etiology ; Pre-Eclampsia - pathology ; Pre-Eclampsia - physiopathology ; Preeclampsia ; Pregnancy ; Pressure measurement ; Pressure measurements ; Protein Isoforms - administration & dosage ; Protein Isoforms - genetics ; Protein Isoforms - physiology ; Protein-tyrosine kinase ; Recombinant Proteins - administration & dosage ; Recombinant Proteins - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Sequence Homology, Amino Acid ; Species Specificity ; Surgery ; Surgical implants ; Survival ; Telemetry ; Tyrosine ; Ultrasonography ; Ultrasound ; Urine ; Vascular Endothelial Growth Factor Receptor-1 - administration & dosage ; Vascular Endothelial Growth Factor Receptor-1 - genetics ; Vascular Endothelial Growth Factor Receptor-1 - physiology</subject><ispartof>PloS one, 2015-04, Vol.10 (4), p.e0119547-e0119547</ispartof><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”) Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-597cb86b5d46b057130b7ce68b07159ce6862745738be64499c992e6243065903</citedby><cites>FETCH-LOGICAL-c592t-597cb86b5d46b057130b7ce68b07159ce6862745738be64499c992e6243065903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393117/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393117/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25860260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kanellopoulos-Langevin, Colette</contributor><creatorcontrib>Szalai, Gabor</creatorcontrib><creatorcontrib>Romero, Roberto</creatorcontrib><creatorcontrib>Chaiworapongsa, Tinnakorn</creatorcontrib><creatorcontrib>Xu, Yi</creatorcontrib><creatorcontrib>Wang, Bing</creatorcontrib><creatorcontrib>Ahn, Hyunyoung</creatorcontrib><creatorcontrib>Xu, Zhonghui</creatorcontrib><creatorcontrib>Chiang, Po Jen</creatorcontrib><creatorcontrib>Sundell, Birgitta</creatorcontrib><creatorcontrib>Wang, Rona</creatorcontrib><creatorcontrib>Jiang, Yang</creatorcontrib><creatorcontrib>Plazyo, Olesya</creatorcontrib><creatorcontrib>Olive, Mary</creatorcontrib><creatorcontrib>Tarca, Adi L</creatorcontrib><creatorcontrib>Dong, Zhong</creatorcontrib><creatorcontrib>Qureshi, Faisal</creatorcontrib><creatorcontrib>Papp, Zoltan</creatorcontrib><creatorcontrib>Hassan, Sonia S</creatorcontrib><creatorcontrib>Hernandez-Andrade, Edgar</creatorcontrib><creatorcontrib>Than, Nandor Gabor</creatorcontrib><title>Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.
Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.
Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).
A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</description><subject>Adenoviruses</subject><subject>Age</subject><subject>Albumin</subject><subject>Amino Acid Sequence</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Aorta</subject><subject>Blood</subject><subject>Blood Pressure</subject><subject>Blood Pressure Monitors</subject><subject>Carotid artery</subject><subject>Catheters</subject><subject>Cell adhesion & migration</subject><subject>Cesarean section</subject><subject>Childrens health</subject><subject>Creatinine</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fetuses</subject><subject>Fluorescence</subject><subject>Gene Expression Profiling</subject><subject>Gestational Age</subject><subject>Green fluorescent protein</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Monitoring</subject><subject>Obstetrics</subject><subject>Pathology</subject><subject>Phenotype</subject><subject>Placenta</subject><subject>Placenta - diagnostic imaging</subject><subject>Placenta - pathology</subject><subject>Placenta - physiopathology</subject><subject>Postpartum</subject><subject>Pre-eclampsia</subject><subject>Pre-Eclampsia - etiology</subject><subject>Pre-Eclampsia - pathology</subject><subject>Pre-Eclampsia - physiopathology</subject><subject>Preeclampsia</subject><subject>Pregnancy</subject><subject>Pressure measurement</subject><subject>Pressure measurements</subject><subject>Protein Isoforms - administration & dosage</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - physiology</subject><subject>Protein-tyrosine kinase</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Sequence Homology, Amino Acid</subject><subject>Species Specificity</subject><subject>Surgery</subject><subject>Surgical implants</subject><subject>Survival</subject><subject>Telemetry</subject><subject>Tyrosine</subject><subject>Ultrasonography</subject><subject>Ultrasound</subject><subject>Urine</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - administration & dosage</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - genetics</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - physiology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAQjRCIlsI_QBCJSy9Z_O34goSqLlSqxAXOluPM7nrl2MF2kPrvSbpp1SJOHnnee_Nm9KrqPUYbTCX-fIxTCsZvxhhggzBWnMkX1TlWlDSCIPrySX1Wvcn5iBCnrRCvqzPCW4GIQOeV307eNx7CvhzqwzSYUI_eWAjF-DpvfWlwA5ib2uW4i2moXegnC7nuXS4u2FIPpsBipB4PEGK5G-dm3NVjArDeDGN2MznUg7Pwtnq1Mz7Du_W9qH5tr39efW9uf3y7ufp621iuSGm4krZrRcd7JjrEJaaokxZE2yGJuVoqQSTjkrYdCMaUskoREIRRJLhC9KL6eNIdfcx6PVTWWEhCWobRgrg5IfpojnpMbjDpTkfj9P1HTHttUnHWgyYIW4Z3BCHcMila1XOOu36WUsRaxWatL-u0qRugX26XjH8m-rwT3EHv4x_NqKIYy1ngchVI8fcEuejBZQvemwBxuvdN0bysXGZ9-gf6_-3YCWVTzDnB7tEMRnoJzwNLL-HRa3hm2oenizySHtJC_wKnL8EE</recordid><startdate>20150410</startdate><enddate>20150410</enddate><creator>Szalai, Gabor</creator><creator>Romero, Roberto</creator><creator>Chaiworapongsa, Tinnakorn</creator><creator>Xu, Yi</creator><creator>Wang, Bing</creator><creator>Ahn, Hyunyoung</creator><creator>Xu, Zhonghui</creator><creator>Chiang, Po Jen</creator><creator>Sundell, Birgitta</creator><creator>Wang, Rona</creator><creator>Jiang, Yang</creator><creator>Plazyo, Olesya</creator><creator>Olive, Mary</creator><creator>Tarca, Adi L</creator><creator>Dong, Zhong</creator><creator>Qureshi, Faisal</creator><creator>Papp, Zoltan</creator><creator>Hassan, Sonia S</creator><creator>Hernandez-Andrade, Edgar</creator><creator>Than, Nandor Gabor</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150410</creationdate><title>Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice</title><author>Szalai, Gabor ; Romero, Roberto ; Chaiworapongsa, Tinnakorn ; Xu, Yi ; Wang, Bing ; Ahn, Hyunyoung ; Xu, Zhonghui ; Chiang, Po Jen ; Sundell, Birgitta ; Wang, Rona ; Jiang, Yang ; Plazyo, Olesya ; Olive, Mary ; Tarca, Adi L ; Dong, Zhong ; Qureshi, Faisal ; Papp, Zoltan ; Hassan, Sonia S ; Hernandez-Andrade, Edgar ; Than, Nandor Gabor</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c592t-597cb86b5d46b057130b7ce68b07159ce6862745738be64499c992e6243065903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenoviruses</topic><topic>Age</topic><topic>Albumin</topic><topic>Amino Acid Sequence</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Aorta</topic><topic>Blood</topic><topic>Blood Pressure</topic><topic>Blood Pressure Monitors</topic><topic>Carotid artery</topic><topic>Catheters</topic><topic>Cell adhesion & migration</topic><topic>Cesarean section</topic><topic>Childrens health</topic><topic>Creatinine</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fetuses</topic><topic>Fluorescence</topic><topic>Gene Expression Profiling</topic><topic>Gestational Age</topic><topic>Green fluorescent protein</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Molecular Sequence Data</topic><topic>Monitoring</topic><topic>Obstetrics</topic><topic>Pathology</topic><topic>Phenotype</topic><topic>Placenta</topic><topic>Placenta - diagnostic imaging</topic><topic>Placenta - pathology</topic><topic>Placenta - physiopathology</topic><topic>Postpartum</topic><topic>Pre-eclampsia</topic><topic>Pre-Eclampsia - etiology</topic><topic>Pre-Eclampsia - pathology</topic><topic>Pre-Eclampsia - physiopathology</topic><topic>Preeclampsia</topic><topic>Pregnancy</topic><topic>Pressure measurement</topic><topic>Pressure measurements</topic><topic>Protein Isoforms - administration & dosage</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - physiology</topic><topic>Protein-tyrosine kinase</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Sequence Homology, Amino Acid</topic><topic>Species Specificity</topic><topic>Surgery</topic><topic>Surgical implants</topic><topic>Survival</topic><topic>Telemetry</topic><topic>Tyrosine</topic><topic>Ultrasonography</topic><topic>Ultrasound</topic><topic>Urine</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - administration & dosage</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - genetics</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Szalai, Gabor</creatorcontrib><creatorcontrib>Romero, Roberto</creatorcontrib><creatorcontrib>Chaiworapongsa, Tinnakorn</creatorcontrib><creatorcontrib>Xu, Yi</creatorcontrib><creatorcontrib>Wang, Bing</creatorcontrib><creatorcontrib>Ahn, Hyunyoung</creatorcontrib><creatorcontrib>Xu, Zhonghui</creatorcontrib><creatorcontrib>Chiang, Po Jen</creatorcontrib><creatorcontrib>Sundell, Birgitta</creatorcontrib><creatorcontrib>Wang, Rona</creatorcontrib><creatorcontrib>Jiang, Yang</creatorcontrib><creatorcontrib>Plazyo, Olesya</creatorcontrib><creatorcontrib>Olive, Mary</creatorcontrib><creatorcontrib>Tarca, Adi L</creatorcontrib><creatorcontrib>Dong, Zhong</creatorcontrib><creatorcontrib>Qureshi, Faisal</creatorcontrib><creatorcontrib>Papp, Zoltan</creatorcontrib><creatorcontrib>Hassan, Sonia S</creatorcontrib><creatorcontrib>Hernandez-Andrade, Edgar</creatorcontrib><creatorcontrib>Than, Nandor Gabor</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Szalai, Gabor</au><au>Romero, Roberto</au><au>Chaiworapongsa, Tinnakorn</au><au>Xu, Yi</au><au>Wang, Bing</au><au>Ahn, Hyunyoung</au><au>Xu, Zhonghui</au><au>Chiang, Po Jen</au><au>Sundell, Birgitta</au><au>Wang, Rona</au><au>Jiang, Yang</au><au>Plazyo, Olesya</au><au>Olive, Mary</au><au>Tarca, Adi L</au><au>Dong, Zhong</au><au>Qureshi, Faisal</au><au>Papp, Zoltan</au><au>Hassan, Sonia S</au><au>Hernandez-Andrade, Edgar</au><au>Than, Nandor Gabor</au><au>Kanellopoulos-Langevin, Colette</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-04-10</date><risdate>2015</risdate><volume>10</volume><issue>4</issue><spage>e0119547</spage><epage>e0119547</epage><pages>e0119547-e0119547</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.
Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.
Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).
A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25860260</pmid><doi>10.1371/journal.pone.0119547</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-04, Vol.10 (4), p.e0119547-e0119547 |
| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenoviruses Age Albumin Amino Acid Sequence Angiogenesis Animal models Animals Aorta Blood Blood Pressure Blood Pressure Monitors Carotid artery Catheters Cell adhesion & migration Cesarean section Childrens health Creatinine Disease Models, Animal Female Fetuses Fluorescence Gene Expression Profiling Gestational Age Green fluorescent protein Green Fluorescent Proteins - genetics Gynecology Humans Hypertension Liver Liver diseases Medical research Medicine Mice Mice, Transgenic Molecular Sequence Data Monitoring Obstetrics Pathology Phenotype Placenta Placenta - diagnostic imaging Placenta - pathology Placenta - physiopathology Postpartum Pre-eclampsia Pre-Eclampsia - etiology Pre-Eclampsia - pathology Pre-Eclampsia - physiopathology Preeclampsia Pregnancy Pressure measurement Pressure measurements Protein Isoforms - administration & dosage Protein Isoforms - genetics Protein Isoforms - physiology Protein-tyrosine kinase Recombinant Proteins - administration & dosage Recombinant Proteins - genetics RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Sequence Homology, Amino Acid Species Specificity Surgery Surgical implants Survival Telemetry Tyrosine Ultrasonography Ultrasound Urine Vascular Endothelial Growth Factor Receptor-1 - administration & dosage Vascular Endothelial Growth Factor Receptor-1 - genetics Vascular Endothelial Growth Factor Receptor-1 - physiology |
| title | Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice |
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