Relationship between hypoxia and downstream pathogenic pathways in preeclampsia
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1080/10641955.2016.1259627 http://hdl.handle.net/11449/162883 |
Resumo: | Defects in angiogenesis and mitochondrial function in the placenta contribute to the pathogenesis of preeclampsia; however upstream regulators of these pathways are not known. It has been argued that placental hypoxia secondary to abnormal spiral artery remodeling may play a causal role in the angiogenic and mitochondrial abnormalities noted in preeclampsia. The aim of this study was to evaluate the relationship between hypoxia-inducible factor-1 (HIF-1) a surrogate of hypoxia, and soluble fms-tyrosine kinase 1 (sFlt1), a circulating anti-angiogenic factor, and microRNA 210 (miR-210), a microRNA that regulates mitochondrial function, in human placentas from preeclamptic and non-hypertensive pregnancies. We first confirmed a 2.5-fold upregulation of HIF-1 protein in placentas from preeclampsia when compared to non-hypertensive controls. Consistent with prior studies, we also observed a 10-fold upregulated sFlt1 mRNA and 2-fold upregulated miR-210 in preeclamptic tissue. Interestingly, while sFlt1 mRNA correlated with miR-210 in preeclampsia (R-2 = 0.77, p = 0.0004), there were no significant correlations between these molecules and HIF1 expression. We conclude that non-hypoxia pathways may be involved in the abnormal angiogenic and metabolic alterations noted in preeclampsia. |
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Relationship between hypoxia and downstream pathogenic pathways in preeclampsiaHIF-1 proteinmiR-210placentapreeclampsiapregnancysFlt1Defects in angiogenesis and mitochondrial function in the placenta contribute to the pathogenesis of preeclampsia; however upstream regulators of these pathways are not known. It has been argued that placental hypoxia secondary to abnormal spiral artery remodeling may play a causal role in the angiogenic and mitochondrial abnormalities noted in preeclampsia. The aim of this study was to evaluate the relationship between hypoxia-inducible factor-1 (HIF-1) a surrogate of hypoxia, and soluble fms-tyrosine kinase 1 (sFlt1), a circulating anti-angiogenic factor, and microRNA 210 (miR-210), a microRNA that regulates mitochondrial function, in human placentas from preeclamptic and non-hypertensive pregnancies. We first confirmed a 2.5-fold upregulation of HIF-1 protein in placentas from preeclampsia when compared to non-hypertensive controls. Consistent with prior studies, we also observed a 10-fold upregulated sFlt1 mRNA and 2-fold upregulated miR-210 in preeclamptic tissue. Interestingly, while sFlt1 mRNA correlated with miR-210 in preeclampsia (R-2 = 0.77, p = 0.0004), there were no significant correlations between these molecules and HIF1 expression. We conclude that non-hypoxia pathways may be involved in the abnormal angiogenic and metabolic alterations noted in preeclampsia.Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USAHarvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA USAHarvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA USAUniv Fed Sao Paulo, Dept Obstet, Sao Paulo, BrazilSao Paulo State Univ, Botucatu Med Sch, Dept Gynecol & Obstet, Sao Paulo, BrazilEmory Sch Med, Dept Gynecol & Obstet, Atlanta, GA USASao Paulo State Univ, Botucatu Med Sch, Dept Gynecol & Obstet, Sao Paulo, BrazilTaylor & Francis IncHarvard Med SchUniversidade Federal de São Paulo (UNIFESP)Universidade Estadual Paulista (Unesp)Emory Sch MedKorkes, Henri AugustoDe Oliveira, Leandro [UNESP]Sass, NelsonSalahuddin, SairaKarumanchi, S. AnanthRajakumar, Augustine2018-11-26T17:34:48Z2018-11-26T17:34:48Z2017-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article145-150application/pdfhttp://dx.doi.org/10.1080/10641955.2016.1259627Hypertension In Pregnancy. Philadelphia: Taylor & Francis Inc, v. 36, n. 2, p. 145-150, 2017.1064-1955http://hdl.handle.net/11449/16288310.1080/10641955.2016.1259627WOS:000403435800005WOS000403435800005.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengHypertension In Pregnancy0,556info:eu-repo/semantics/openAccess2024-08-16T14:07:08Zoai:repositorio.unesp.br:11449/162883Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-16T14:07:08Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia |
title |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia |
spellingShingle |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia Korkes, Henri Augusto HIF-1 protein miR-210 placenta preeclampsia pregnancy sFlt1 |
title_short |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia |
title_full |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia |
title_fullStr |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia |
title_full_unstemmed |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia |
title_sort |
Relationship between hypoxia and downstream pathogenic pathways in preeclampsia |
author |
Korkes, Henri Augusto |
author_facet |
Korkes, Henri Augusto De Oliveira, Leandro [UNESP] Sass, Nelson Salahuddin, Saira Karumanchi, S. Ananth Rajakumar, Augustine |
author_role |
author |
author2 |
De Oliveira, Leandro [UNESP] Sass, Nelson Salahuddin, Saira Karumanchi, S. Ananth Rajakumar, Augustine |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Harvard Med Sch Universidade Federal de São Paulo (UNIFESP) Universidade Estadual Paulista (Unesp) Emory Sch Med |
dc.contributor.author.fl_str_mv |
Korkes, Henri Augusto De Oliveira, Leandro [UNESP] Sass, Nelson Salahuddin, Saira Karumanchi, S. Ananth Rajakumar, Augustine |
dc.subject.por.fl_str_mv |
HIF-1 protein miR-210 placenta preeclampsia pregnancy sFlt1 |
topic |
HIF-1 protein miR-210 placenta preeclampsia pregnancy sFlt1 |
description |
Defects in angiogenesis and mitochondrial function in the placenta contribute to the pathogenesis of preeclampsia; however upstream regulators of these pathways are not known. It has been argued that placental hypoxia secondary to abnormal spiral artery remodeling may play a causal role in the angiogenic and mitochondrial abnormalities noted in preeclampsia. The aim of this study was to evaluate the relationship between hypoxia-inducible factor-1 (HIF-1) a surrogate of hypoxia, and soluble fms-tyrosine kinase 1 (sFlt1), a circulating anti-angiogenic factor, and microRNA 210 (miR-210), a microRNA that regulates mitochondrial function, in human placentas from preeclamptic and non-hypertensive pregnancies. We first confirmed a 2.5-fold upregulation of HIF-1 protein in placentas from preeclampsia when compared to non-hypertensive controls. Consistent with prior studies, we also observed a 10-fold upregulated sFlt1 mRNA and 2-fold upregulated miR-210 in preeclamptic tissue. Interestingly, while sFlt1 mRNA correlated with miR-210 in preeclampsia (R-2 = 0.77, p = 0.0004), there were no significant correlations between these molecules and HIF1 expression. We conclude that non-hypoxia pathways may be involved in the abnormal angiogenic and metabolic alterations noted in preeclampsia. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-01-01 2018-11-26T17:34:48Z 2018-11-26T17:34:48Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1080/10641955.2016.1259627 Hypertension In Pregnancy. Philadelphia: Taylor & Francis Inc, v. 36, n. 2, p. 145-150, 2017. 1064-1955 http://hdl.handle.net/11449/162883 10.1080/10641955.2016.1259627 WOS:000403435800005 WOS000403435800005.pdf |
url |
http://dx.doi.org/10.1080/10641955.2016.1259627 http://hdl.handle.net/11449/162883 |
identifier_str_mv |
Hypertension In Pregnancy. Philadelphia: Taylor & Francis Inc, v. 36, n. 2, p. 145-150, 2017. 1064-1955 10.1080/10641955.2016.1259627 WOS:000403435800005 WOS000403435800005.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Hypertension In Pregnancy 0,556 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
145-150 application/pdf |
dc.publisher.none.fl_str_mv |
Taylor & Francis Inc |
publisher.none.fl_str_mv |
Taylor & Francis Inc |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128154600996864 |