Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.

Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Agua Sobrino, Manuel Mata, Andrés Laguna-Fernandez, Susana Novella, Pilar J Oviedo, Miguel Angel García-Pérez, Juan J Tarín, Antonio Cano, Carlos Hermenegildo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a11cd2cfd35a4ce9b53d1a8bf6cf4a66
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a11cd2cfd35a4ce9b53d1a8bf6cf4a66
record_format	dspace
spelling	oai:doaj.org-article:a11cd2cfd35a4ce9b53d1a8bf6cf4a662021-11-25T06:27:25ZEstradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.1932-620310.1371/journal.pone.0008242https://doaj.org/article/a11cd2cfd35a4ce9b53d1a8bf6cf4a662009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20011585/?tool=EBIhttps://doaj.org/toc/1932-6203Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cytoskeleton signaling, pentose phosphate pathway, axonal guidance signaling and integrin signaling were the top-five canonical pathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxygenase (COX)1, dimethylarginine dimethylaminohydrolase (DDAH)2, phospholipase A2 group IV (PLA2G4) B, and 7-dehydrocholesterol reductase were up-regulated by estradiol in a dose-dependent and estrogen receptor-dependent way, whereas COX2, DDAH1 and PLA2G4A remained unaltered. Moreover, estradiol-induced COX1 gene expression resulted in increased COX1 protein content and enhanced prostacyclin production. DDAH2 protein content was also increased, which in turn decreased asymmetric dimethylarginine concentration and increased NO release. All stimulated effects of estradiol on gene and protein expression were estrogen receptor-dependent, since were abolished in the presence of the estrogen receptor antagonist ICI 182780. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes.Agua SobrinoManuel MataAndrés Laguna-FernandezSusana NovellaPilar J OviedoMiguel Angel García-PérezJuan J TarínAntonio CanoCarlos HermenegildoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8242 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agua Sobrino Manuel Mata Andrés Laguna-Fernandez Susana Novella Pilar J Oviedo Miguel Angel García-Pérez Juan J Tarín Antonio Cano Carlos Hermenegildo Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
description	Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cytoskeleton signaling, pentose phosphate pathway, axonal guidance signaling and integrin signaling were the top-five canonical pathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxygenase (COX)1, dimethylarginine dimethylaminohydrolase (DDAH)2, phospholipase A2 group IV (PLA2G4) B, and 7-dehydrocholesterol reductase were up-regulated by estradiol in a dose-dependent and estrogen receptor-dependent way, whereas COX2, DDAH1 and PLA2G4A remained unaltered. Moreover, estradiol-induced COX1 gene expression resulted in increased COX1 protein content and enhanced prostacyclin production. DDAH2 protein content was also increased, which in turn decreased asymmetric dimethylarginine concentration and increased NO release. All stimulated effects of estradiol on gene and protein expression were estrogen receptor-dependent, since were abolished in the presence of the estrogen receptor antagonist ICI 182780. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes.
format	article
author	Agua Sobrino Manuel Mata Andrés Laguna-Fernandez Susana Novella Pilar J Oviedo Miguel Angel García-Pérez Juan J Tarín Antonio Cano Carlos Hermenegildo
author_facet	Agua Sobrino Manuel Mata Andrés Laguna-Fernandez Susana Novella Pilar J Oviedo Miguel Angel García-Pérez Juan J Tarín Antonio Cano Carlos Hermenegildo
author_sort	Agua Sobrino
title	Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
title_short	Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
title_full	Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
title_fullStr	Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
title_full_unstemmed	Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
title_sort	estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/a11cd2cfd35a4ce9b53d1a8bf6cf4a66
work_keys_str_mv	AT aguasobrino estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT manuelmata estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT andreslagunafernandez estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT susananovella estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT pilarjoviedo estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT miguelangelgarciaperez estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT juanjtarin estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT antoniocano estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells AT carloshermenegildo estradiolstimulatesvasodilatoryandmetabolicpathwaysinculturedhumanendothelialcells
_version_	1718413698448490496

Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.

Ejemplares similares