BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis
Myocarditis is an inflammatory heart disease that leads to dilated cardiomyopathy (DCM) and heart failure. Sex hormones play an important role in the development of myocarditis with testosterone driving disease in males and estrogen being cardioprotective in females. The human population is widely e...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00598/full |
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| author | Katelyn Ann Bruno Katelyn Ann Bruno Katelyn Ann Bruno Katelyn Ann Bruno Jessica Elizabeth Mathews Alex Lingyun Yang Alex Lingyun Yang J. Augusto Frisancho Ashley Jennie Scott Henry David Greyner Frank Anthony Molina Merci Shekinah Greenaway George Maxwell Cooper Adriana Bucek Andrea Carolina Morales-Lara Anneliese Ruth Hill Anna Alisa Mease Damian Nicolas Di Florio Damian Nicolas Di Florio John Michael Sousou Alexandria Christine Coronado Allison Ray Stafford DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather |
| author_facet | Katelyn Ann Bruno Katelyn Ann Bruno Katelyn Ann Bruno Katelyn Ann Bruno Jessica Elizabeth Mathews Alex Lingyun Yang Alex Lingyun Yang J. Augusto Frisancho Ashley Jennie Scott Henry David Greyner Frank Anthony Molina Merci Shekinah Greenaway George Maxwell Cooper Adriana Bucek Andrea Carolina Morales-Lara Anneliese Ruth Hill Anna Alisa Mease Damian Nicolas Di Florio Damian Nicolas Di Florio John Michael Sousou Alexandria Christine Coronado Allison Ray Stafford DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather |
| author_sort | Katelyn Ann Bruno |
| collection | DOAJ |
| description | Myocarditis is an inflammatory heart disease that leads to dilated cardiomyopathy (DCM) and heart failure. Sex hormones play an important role in the development of myocarditis with testosterone driving disease in males and estrogen being cardioprotective in females. The human population is widely exposed to the endocrine disruptor bisphenol A (BPA) from plastics such as water bottles, plastic food containers, copy paper, and receipts. Several clinical and numerous animal studies have found an association between elevated BPA levels and cardiovascular disease. A recent report found elevated levels of BPA in the serum of patients with DCM compared to healthy controls. In this study we examined whether exposure to BPA for 2 weeks prior to viral infection and leading up to myocarditis at day 10 altered inflammation in female BALB/c mice housed in standard plastic cages/water bottles with soy-free food and bedding. We found that a human relevant dose of BPA (25 μg/L) in drinking water, with an estimated exposure of 5 μg BPA/kg BW, significantly increased myocarditis and pericarditis compared to control water without altering viral genome levels in the heart. BPA exposure activated ERα and ERβ in the spleen 24 h after infection and phosphorylated ERα and ERβ during myocarditis, but decreased ERα and increased ERβ mRNA in the heart as measured by qRT-PCR. Exposure to BPA significantly increased CD4+ T cells, IFNγ, IL-17A, TLR4, caspase-1, and IL-1β in the heart. BPA exposure also increased cardiac fibrosis compared to controls. Mast cells, which are associated with cardiac remodeling, were found to increase in number and degranulation, particularly along the pericardium. Interestingly, plastic caging/water bottle exposure alone led to increased mast cell numbers, pericardial degranulation and fibrosis in female BALB/c mice compared to animals housed in glass cages/water bottles with soy-free food and bedding. These data suggest that BPA exposure may increase the risk of developing myocarditis after a viral infection in women. |
| first_indexed | 2024-12-12T02:07:06Z |
| format | Article |
| id | doaj.art-329d48aa49844f57b376958870eed875 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-12T02:07:06Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-329d48aa49844f57b376958870eed8752022-12-22T00:42:02ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-09-011010.3389/fendo.2019.00598463043BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and FibrosisKatelyn Ann Bruno0Katelyn Ann Bruno1Katelyn Ann Bruno2Katelyn Ann Bruno3Jessica Elizabeth Mathews4Alex Lingyun Yang5Alex Lingyun Yang6J. Augusto Frisancho7Ashley Jennie Scott8Henry David Greyner9Frank Anthony Molina10Merci Shekinah Greenaway11George Maxwell Cooper12Adriana Bucek13Andrea Carolina Morales-Lara14Anneliese Ruth Hill15Anna Alisa Mease16Damian Nicolas Di Florio17Damian Nicolas Di Florio18John Michael Sousou19Alexandria Christine Coronado20Allison Ray Stafford21DeLisa Fairweather22DeLisa Fairweather23DeLisa Fairweather24DeLisa Fairweather25Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Immunology, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Immunology, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesMyocarditis is an inflammatory heart disease that leads to dilated cardiomyopathy (DCM) and heart failure. Sex hormones play an important role in the development of myocarditis with testosterone driving disease in males and estrogen being cardioprotective in females. The human population is widely exposed to the endocrine disruptor bisphenol A (BPA) from plastics such as water bottles, plastic food containers, copy paper, and receipts. Several clinical and numerous animal studies have found an association between elevated BPA levels and cardiovascular disease. A recent report found elevated levels of BPA in the serum of patients with DCM compared to healthy controls. In this study we examined whether exposure to BPA for 2 weeks prior to viral infection and leading up to myocarditis at day 10 altered inflammation in female BALB/c mice housed in standard plastic cages/water bottles with soy-free food and bedding. We found that a human relevant dose of BPA (25 μg/L) in drinking water, with an estimated exposure of 5 μg BPA/kg BW, significantly increased myocarditis and pericarditis compared to control water without altering viral genome levels in the heart. BPA exposure activated ERα and ERβ in the spleen 24 h after infection and phosphorylated ERα and ERβ during myocarditis, but decreased ERα and increased ERβ mRNA in the heart as measured by qRT-PCR. Exposure to BPA significantly increased CD4+ T cells, IFNγ, IL-17A, TLR4, caspase-1, and IL-1β in the heart. BPA exposure also increased cardiac fibrosis compared to controls. Mast cells, which are associated with cardiac remodeling, were found to increase in number and degranulation, particularly along the pericardium. Interestingly, plastic caging/water bottle exposure alone led to increased mast cell numbers, pericardial degranulation and fibrosis in female BALB/c mice compared to animals housed in glass cages/water bottles with soy-free food and bedding. These data suggest that BPA exposure may increase the risk of developing myocarditis after a viral infection in women.https://www.frontiersin.org/article/10.3389/fendo.2019.00598/fullmyocarditisendocrine disruptorbisphenol Aestrogen receptormast cells |
| spellingShingle | Katelyn Ann Bruno Katelyn Ann Bruno Katelyn Ann Bruno Katelyn Ann Bruno Jessica Elizabeth Mathews Alex Lingyun Yang Alex Lingyun Yang J. Augusto Frisancho Ashley Jennie Scott Henry David Greyner Frank Anthony Molina Merci Shekinah Greenaway George Maxwell Cooper Adriana Bucek Andrea Carolina Morales-Lara Anneliese Ruth Hill Anna Alisa Mease Damian Nicolas Di Florio Damian Nicolas Di Florio John Michael Sousou Alexandria Christine Coronado Allison Ray Stafford DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis Frontiers in Endocrinology myocarditis endocrine disruptor bisphenol A estrogen receptor mast cells |
| title | BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis |
| title_full | BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis |
| title_fullStr | BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis |
| title_full_unstemmed | BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis |
| title_short | BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis |
| title_sort | bpa alters estrogen receptor expression in the heart after viral infection activating cardiac mast cells and t cells leading to perimyocarditis and fibrosis |
| topic | myocarditis endocrine disruptor bisphenol A estrogen receptor mast cells |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00598/full |
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