Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión

The association between reduced foetal growth and adult health has risen as a feasible explanation for non-Mendelian diseases, such as hypertension and type-2 diabetes. Epigenetic mechanisms (i.e. DNA methylation, histone post-translational modifications) have been broadly suggested to be involved i...

Descripción completa

Detalles Bibliográficos
Autor: Krause-Leyton, Bernardo Javier
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2012
País:Chile
Idioma:inglés
OAI Identifier:oai:repositorio.anid.cl:10533/179952
Acceso en línea:http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
https://hdl.handle.net/10533/179952
Access Level:acceso abierto
id CL_187adcd198c1aa608b064f2e438cc6ef
oai_identifier_str oai:repositorio.anid.cl:10533/179952
network_acronym_str CL
network_name_str Chile
repository_id_str
dc.title.none.fl_str_mv Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
title Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
spellingShingle Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
Krause-Leyton, Bernardo Javier
title_short Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
title_full Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
title_fullStr Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
title_full_unstemmed Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
title_sort Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictión
dc.creator.none.fl_str_mv Krause-Leyton, Bernardo Javier
author Krause-Leyton, Bernardo Javier
author_facet Krause-Leyton, Bernardo Javier
author_role author
dc.contributor.advisor.none.fl_str_mv Casanello-T, Paola
Sobrevia-L, Luis
dc.contributor.institution.none.fl_str_mv Pontificia Universidad Católica de Chile
description The association between reduced foetal growth and adult health has risen as a feasible explanation for non-Mendelian diseases, such as hypertension and type-2 diabetes. Epigenetic mechanisms (i.e. DNA methylation, histone post-translational modifications) have been broadly suggested to be involved in this process, 'recording' normal and abnormal perinatalstimuli and shaping long term gene expression in the cardiovascular system. In this context, cultured human umbilical endothelial cells (HUVEC) derived from pregnancies with intrauterine growth restriction (IUGR) present an altered expression of proteins related withthe L-arginine/nitric oxide metabolism (i.e. eNOS and arginase-2), suggesting an early onset of endothelial dysfunction. This project studied whether arginase-2 participates in the IUGR placental vascular dysfunction, counteracting with eNOS activity in umbilical arteries andveins, as well as chorionic arteries. Additionally, the expression of both proteins in cultured endothelial cells from chorionic (PLAEC), umbilical arteries (HUAEC), and HUVEC wasanalysed. In order to determine the participation of epigenetic mechanisms, the effect of DNA methylation and histone acetylation activities on basal eNOS and arginase-2 expression was studied, as well as the presence of altered methylation status in the NOS3 (eN OS) and ARG2 (arginase-2) promoters. In IUGR vessels eNOS-dependent relaxation was reduced, being improved by arginase-inhibition. Arginase-2 protein expression was increased IUGR HUVEC, without changes in HUAEC and PLAEC. Additionally, eNOS expression was reduced in HUVEC and augmented in HUAEC and PLAEC; however there was a generalized reductionin the in vitro eNOS activation (Ser1177-P-eNOS). Inhibition of heritable DNA methylation restored to normal values the eNOS expression in IUGR EC; however it further increased the arginase-2 expression in IUGR HUVEC, without effects on HUAEC. The DNA methylation pattem in NOS3 promoter showed a limited number of CpGs differentially methylated innormal HUAEC, PLAEC and HUVEC, with differences between arteries and vein endothelial cells. Noteworthy, the changes in NOS3 promoter DNA methylation in IUGR endothelial cells occurred in the same CpGs that were differentially methylated in normal arteries (HUAEC andPLAEC) and HUVEC. In contrast, DNA methylation pattem in ARG2 promoter wascomparable in normal endothelial cells, but changes in DNA methylation in IUGR cells were similar only between HUAEC and PLAEC. Inhibition of histone deacetylation reduced eN OS mRNA and protein levels, and increased arginase-2 expression in IUGR HUAEC. Altogetherthese data showed that arginase-2 and eNOS expression are differentially regulated in IUGR endothelial cells, being their expression basally controlled by epigenetic mechanisms thatoperate in a cell- and gene- specific manner.
publishDate 2012
dc.date.start.none.fl_str_mv 2012
dc.date.issued.none.fl_str_mv 2014
dc.date.accessioned.none.fl_str_mv 2017-03-28T14:03:24Z
2022-08-17T22:18:33Z
dc.date.available.none.fl_str_mv 2017-03-28T14:03:24Z
2022-08-17T22:18:33Z
dc.type.none.fl_str_mv Tesis Doctorado
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.openaire.none.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.tesis.none.fl_str_mv Tesis
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10533/179952
url http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
https://hdl.handle.net/10533/179952
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv instname: Conicyt
reponame: Repositorio Digital RI2.0
instname: Conicyt
reponame: Repositorio Digital RI2.0
dc.relation.program.none.fl_str_mv handle/10533/108040
dc.relation.projectid.none.fl_str_mv info:eu-repo/grantAgreement/PFCHA-Becas/RI20
dc.relation.set.none.fl_str_mv info:eu-repo/semantics/dataset/hdl.handle.net/10533/93488
dc.rights.none.fl_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
dc.rights.driver.none.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
eu_rights_str_mv openAccess
dc.coverage.spatial.none.fl_str_mv Santiago
bitstream.url.fl_str_mv https://repositorio.anid.cl/bitstreams/0e361dc9-a709-493e-898b-3c400f6650e3/download
https://repositorio.anid.cl/bitstreams/eb16897b-1196-40c9-b855-a69b7f4ff1c1/download
https://repositorio.anid.cl/bitstreams/b7ef03ee-9d6b-4594-a38f-f02f79f8b484/download
bitstream.checksum.fl_str_mv 005ac2762f852500d51ea6a1b068dbbe
53b476ed8a5bd284c596e0bf00580502
c77a28717ab43aaf34a25a5fe77b48ef
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositorio ANID
repository.mail.fl_str_mv aletelier@anid.cl
_version_ 1843518823775338496
spelling Pontificia Universidad Católica de ChileKrause-Leyton, Bernardo Javier2014https://hdl.handle.net/10533/179952http://purl.org/coar/access_right/c_abf2Epigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictiónCasanello-T, PaolaSobrevia-L, LuisPontificia Universidad Católica de ChilechiSantiagoKrause-Leyton, Bernardo Javier2017-03-28T14:03:24Z2022-08-17T22:18:33Z2017-03-28T14:03:24Z2022-08-17T22:18:33Z20142012The association between reduced foetal growth and adult health has risen as a feasible explanation for non-Mendelian diseases, such as hypertension and type-2 diabetes. Epigenetic mechanisms (i.e. DNA methylation, histone post-translational modifications) have been broadly suggested to be involved in this process, 'recording' normal and abnormal perinatalstimuli and shaping long term gene expression in the cardiovascular system. In this context, cultured human umbilical endothelial cells (HUVEC) derived from pregnancies with intrauterine growth restriction (IUGR) present an altered expression of proteins related withthe L-arginine/nitric oxide metabolism (i.e. eNOS and arginase-2), suggesting an early onset of endothelial dysfunction. This project studied whether arginase-2 participates in the IUGR placental vascular dysfunction, counteracting with eNOS activity in umbilical arteries andveins, as well as chorionic arteries. Additionally, the expression of both proteins in cultured endothelial cells from chorionic (PLAEC), umbilical arteries (HUAEC), and HUVEC wasanalysed. In order to determine the participation of epigenetic mechanisms, the effect of DNA methylation and histone acetylation activities on basal eNOS and arginase-2 expression was studied, as well as the presence of altered methylation status in the NOS3 (eN OS) and ARG2 (arginase-2) promoters. In IUGR vessels eNOS-dependent relaxation was reduced, being improved by arginase-inhibition. Arginase-2 protein expression was increased IUGR HUVEC, without changes in HUAEC and PLAEC. Additionally, eNOS expression was reduced in HUVEC and augmented in HUAEC and PLAEC; however there was a generalized reductionin the in vitro eNOS activation (Ser1177-P-eNOS). Inhibition of heritable DNA methylation restored to normal values the eNOS expression in IUGR EC; however it further increased the arginase-2 expression in IUGR HUVEC, without effects on HUAEC. The DNA methylation pattem in NOS3 promoter showed a limited number of CpGs differentially methylated innormal HUAEC, PLAEC and HUVEC, with differences between arteries and vein endothelial cells. Noteworthy, the changes in NOS3 promoter DNA methylation in IUGR endothelial cells occurred in the same CpGs that were differentially methylated in normal arteries (HUAEC andPLAEC) and HUVEC. In contrast, DNA methylation pattem in ARG2 promoter wascomparable in normal endothelial cells, but changes in DNA methylation in IUGR cells were similar only between HUAEC and PLAEC. Inhibition of histone deacetylation reduced eN OS mRNA and protein levels, and increased arginase-2 expression in IUGR HUAEC. Altogetherthese data showed that arginase-2 and eNOS expression are differentially regulated in IUGR endothelial cells, being their expression basally controlled by epigenetic mechanisms thatoperate in a cell- and gene- specific manner.PFCHA-BecasDoctorado en Ciencias Biológicas Mención Ciencias Fisiológicas133p.PFCHA-BecasTERMINADAhttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/https://hdl.handle.net/10533/179952enginstname: Conicytreponame: Repositorio Digital RI2.0instname: Conicytreponame: Repositorio Digital RI2.0handle/10533/108040info:eu-repo/grantAgreement/PFCHA-Becas/RI20info:eu-repo/semantics/dataset/hdl.handle.net/10533/93488Atribución-NoComercial-SinDerivadas 3.0 Chileinfo:eu-repo/semantics/openAccessEpigenetic mechanisms implicated in the programming of endothelial dysfunctión in foetuses with intrauterine growth restrictiónTesis Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionTesisTesishttps://hdl.handle.net/10533/179952PFCHA-BecasORIGINALKRAUSE_BERNARDO_2183D.pdfapplication/pdf39811660https://repositorio.anid.cl/bitstreams/0e361dc9-a709-493e-898b-3c400f6650e3/download005ac2762f852500d51ea6a1b068dbbeMD51TEXTKRAUSE_BERNARDO_2183D.pdf.txtExtracted texttext/plain193054https://repositorio.anid.cl/bitstreams/eb16897b-1196-40c9-b855-a69b7f4ff1c1/download53b476ed8a5bd284c596e0bf00580502MD52THUMBNAILKRAUSE_BERNARDO_2183D.pdf.jpgIM Thumbnailimage/jpeg1959https://repositorio.anid.cl/bitstreams/b7ef03ee-9d6b-4594-a38f-f02f79f8b484/downloadc77a28717ab43aaf34a25a5fe77b48efMD5310533/179952oai:repositorio.anid.cl:10533/1799522023-07-24 05:22:18.828https://repositorio.anid.clRepositorio ANIDaletelier@anid.cl
score 15,811543

Similares en LA Referencia