Cargando…
Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability
In the presence of established atherosclerosis, estrogens are potentially harmful. MMP-2 and MMP-9, their inhibitors (TIMP-2 and TIMP-1), RANK, RANKL, OPG, MCP-1, lysyl oxidase (LOX), PDGF-β, and ADAMTS-4 play critical roles in plaque instability/rupture. We aimed to investigate (i) the effect of es...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506323/ https://www.ncbi.nlm.nih.gov/pubmed/36142876 http://dx.doi.org/10.3390/ijms231810960 |
_version_ | 1784796694619095040 |
---|---|
author | Nasiri-Ansari, Narjes Spilioti, Eliana Kyrou, Ioannis Kalotychou, Vassiliki Chatzigeorgiou, Antonios Sanoudou, Despina Dahlman-Wright, Karin Randeva, Harpal S. Papavassiliou, Athanasios G. Moutsatsou, Paraskevi Kassi, Eva |
author_facet | Nasiri-Ansari, Narjes Spilioti, Eliana Kyrou, Ioannis Kalotychou, Vassiliki Chatzigeorgiou, Antonios Sanoudou, Despina Dahlman-Wright, Karin Randeva, Harpal S. Papavassiliou, Athanasios G. Moutsatsou, Paraskevi Kassi, Eva |
author_sort | Nasiri-Ansari, Narjes |
collection | PubMed |
description | In the presence of established atherosclerosis, estrogens are potentially harmful. MMP-2 and MMP-9, their inhibitors (TIMP-2 and TIMP-1), RANK, RANKL, OPG, MCP-1, lysyl oxidase (LOX), PDGF-β, and ADAMTS-4 play critical roles in plaque instability/rupture. We aimed to investigate (i) the effect of estradiol on the expression of the abovementioned molecules in endothelial cells, (ii) which type(s) of estrogen receptors mediate these effects, and (iii) the role of p21 in the estrogen-mediated regulation of the aforementioned factors. Human aortic endothelial cells (HAECs) were cultured with estradiol in the presence or absence of TNF-α. The expression of the aforementioned molecules was assessed by qRT-PCR and ELISA. Zymography was also performed. The experiments were repeated in either ERα- or ERβ-transfected HAECs and after silencing p21. HAECs expressed only the GPR-30 estrogen receptor. Estradiol, at low concentrations, decreased MMP-2 activity by 15-fold, increased LOX expression by 2-fold via GPR-30, and reduced MCP-1 expression by 3.5-fold via ERβ. The overexpression of ERα increased MCP-1 mRNA expression by 2.5-fold. In a low-grade inflammation state, lower concentrations of estradiol induced the mRNA expression of MCP-1 (3.4-fold) and MMP-9 (7.5-fold) and increased the activity of MMP-2 (1.7-fold) via GPR-30. Moreover, p21 silencing resulted in equivocal effects on the expression of the abovementioned molecules. Estradiol induced different effects regarding atherogenic plaque instability through different ERs. The balance of the expression of the various ER subtypes may play an important role in the paradoxical characterization of estrogens as both beneficial and harmful. |
format | Online Article Text |
id | pubmed-9506323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95063232022-09-24 Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability Nasiri-Ansari, Narjes Spilioti, Eliana Kyrou, Ioannis Kalotychou, Vassiliki Chatzigeorgiou, Antonios Sanoudou, Despina Dahlman-Wright, Karin Randeva, Harpal S. Papavassiliou, Athanasios G. Moutsatsou, Paraskevi Kassi, Eva Int J Mol Sci Article In the presence of established atherosclerosis, estrogens are potentially harmful. MMP-2 and MMP-9, their inhibitors (TIMP-2 and TIMP-1), RANK, RANKL, OPG, MCP-1, lysyl oxidase (LOX), PDGF-β, and ADAMTS-4 play critical roles in plaque instability/rupture. We aimed to investigate (i) the effect of estradiol on the expression of the abovementioned molecules in endothelial cells, (ii) which type(s) of estrogen receptors mediate these effects, and (iii) the role of p21 in the estrogen-mediated regulation of the aforementioned factors. Human aortic endothelial cells (HAECs) were cultured with estradiol in the presence or absence of TNF-α. The expression of the aforementioned molecules was assessed by qRT-PCR and ELISA. Zymography was also performed. The experiments were repeated in either ERα- or ERβ-transfected HAECs and after silencing p21. HAECs expressed only the GPR-30 estrogen receptor. Estradiol, at low concentrations, decreased MMP-2 activity by 15-fold, increased LOX expression by 2-fold via GPR-30, and reduced MCP-1 expression by 3.5-fold via ERβ. The overexpression of ERα increased MCP-1 mRNA expression by 2.5-fold. In a low-grade inflammation state, lower concentrations of estradiol induced the mRNA expression of MCP-1 (3.4-fold) and MMP-9 (7.5-fold) and increased the activity of MMP-2 (1.7-fold) via GPR-30. Moreover, p21 silencing resulted in equivocal effects on the expression of the abovementioned molecules. Estradiol induced different effects regarding atherogenic plaque instability through different ERs. The balance of the expression of the various ER subtypes may play an important role in the paradoxical characterization of estrogens as both beneficial and harmful. MDPI 2022-09-19 /pmc/articles/PMC9506323/ /pubmed/36142876 http://dx.doi.org/10.3390/ijms231810960 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nasiri-Ansari, Narjes Spilioti, Eliana Kyrou, Ioannis Kalotychou, Vassiliki Chatzigeorgiou, Antonios Sanoudou, Despina Dahlman-Wright, Karin Randeva, Harpal S. Papavassiliou, Athanasios G. Moutsatsou, Paraskevi Kassi, Eva Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability |
title | Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability |
title_full | Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability |
title_fullStr | Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability |
title_full_unstemmed | Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability |
title_short | Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability |
title_sort | estrogen receptor subtypes elicit a distinct gene expression profile of endothelial-derived factors implicated in atherosclerotic plaque vulnerability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506323/ https://www.ncbi.nlm.nih.gov/pubmed/36142876 http://dx.doi.org/10.3390/ijms231810960 |
work_keys_str_mv | AT nasiriansarinarjes estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT spiliotieliana estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT kyrouioannis estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT kalotychouvassiliki estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT chatzigeorgiouantonios estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT sanoudoudespina estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT dahlmanwrightkarin estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT randevaharpals estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT papavassiliouathanasiosg estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT moutsatsouparaskevi estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability AT kassieva estrogenreceptorsubtypeselicitadistinctgeneexpressionprofileofendothelialderivedfactorsimplicatedinatheroscleroticplaquevulnerability |