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Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells
Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascu...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557363/ https://www.ncbi.nlm.nih.gov/pubmed/28809938 http://dx.doi.org/10.1371/journal.pone.0182945 |
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author | Xie, Weiguo Ren, Mingming Li, Ling Zhu, Yin Chu, Zhigang Zhu, Zhigang Ruan, Qiongfang Lou, Wenting Zhang, Haimou Han, Zhen Huang, Xiaodong Xiang, Wei Wang, Tao Yao, Paul |
author_facet | Xie, Weiguo Ren, Mingming Li, Ling Zhu, Yin Chu, Zhigang Zhu, Zhigang Ruan, Qiongfang Lou, Wenting Zhang, Haimou Han, Zhen Huang, Xiaodong Xiang, Wei Wang, Tao Yao, Paul |
author_sort | Xie, Weiguo |
collection | PubMed |
description | Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascular function in offspring is still unknown. Our preliminary results showed that perinatal testosterone exposure in mice induces estrogen receptor β (ERβ) suppression in endothelial progenitor cells (EPCs) in offspring but not mothers, while estradiol (E2) had no effect. Further investigation showed that ERβ suppression is due to perinatal testosterone exposure-induced epigenetic changes with altered DNA methylation on the ERβ promoter. During aging, EPCs with ERβ suppression mobilize to the vascular wall, differentiate into ERβ-suppressed mouse endothelial cells (MECs) with downregulated expression of SOD2 (mitochondrial superoxide dismutase) and ERRα (estrogen-related receptor α). This results in reactive oxygen species (ROS) generation and DNA damage, and the dysfunction of mitochondria and fatty acid metabolism, subsequently potentiating vascular dysfunction. Bone marrow transplantation of EPCs that overexpressed with either ERβ or a SIRT1 single mutant SIRT1-C152(D) that could modulate SIRT1 phosphorylation significantly ameliorated vascular dysfunction, while ERβ knockdown worsened the problem. We conclude that perinatal testosterone exposure potentiates vascular dysfunction through ERβ suppression in EPCs. |
format | Online Article Text |
id | pubmed-5557363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55573632017-08-25 Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells Xie, Weiguo Ren, Mingming Li, Ling Zhu, Yin Chu, Zhigang Zhu, Zhigang Ruan, Qiongfang Lou, Wenting Zhang, Haimou Han, Zhen Huang, Xiaodong Xiang, Wei Wang, Tao Yao, Paul PLoS One Research Article Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascular function in offspring is still unknown. Our preliminary results showed that perinatal testosterone exposure in mice induces estrogen receptor β (ERβ) suppression in endothelial progenitor cells (EPCs) in offspring but not mothers, while estradiol (E2) had no effect. Further investigation showed that ERβ suppression is due to perinatal testosterone exposure-induced epigenetic changes with altered DNA methylation on the ERβ promoter. During aging, EPCs with ERβ suppression mobilize to the vascular wall, differentiate into ERβ-suppressed mouse endothelial cells (MECs) with downregulated expression of SOD2 (mitochondrial superoxide dismutase) and ERRα (estrogen-related receptor α). This results in reactive oxygen species (ROS) generation and DNA damage, and the dysfunction of mitochondria and fatty acid metabolism, subsequently potentiating vascular dysfunction. Bone marrow transplantation of EPCs that overexpressed with either ERβ or a SIRT1 single mutant SIRT1-C152(D) that could modulate SIRT1 phosphorylation significantly ameliorated vascular dysfunction, while ERβ knockdown worsened the problem. We conclude that perinatal testosterone exposure potentiates vascular dysfunction through ERβ suppression in EPCs. Public Library of Science 2017-08-15 /pmc/articles/PMC5557363/ /pubmed/28809938 http://dx.doi.org/10.1371/journal.pone.0182945 Text en © 2017 Xie et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Xie, Weiguo Ren, Mingming Li, Ling Zhu, Yin Chu, Zhigang Zhu, Zhigang Ruan, Qiongfang Lou, Wenting Zhang, Haimou Han, Zhen Huang, Xiaodong Xiang, Wei Wang, Tao Yao, Paul Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells |
title | Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells |
title_full | Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells |
title_fullStr | Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells |
title_full_unstemmed | Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells |
title_short | Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells |
title_sort | perinatal testosterone exposure potentiates vascular dysfunction by erβ suppression in endothelial progenitor cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557363/ https://www.ncbi.nlm.nih.gov/pubmed/28809938 http://dx.doi.org/10.1371/journal.pone.0182945 |
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