BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis

Katelyn Ann Bruno, Jessica Elizabeth Mathews, 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, John Michael Sousou, Alexandria Christine Coronado, Allison Ray Stafford, De Lisa Fairweather

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number598
JournalFrontiers in Endocrinology
Volume10
DOIs
StatePublished - Sep 4 2019

Fingerprint

Virus Diseases
Mast Cells
Estrogen Receptors
Fibrosis
T-Lymphocytes
Myocarditis
Plastics
Water
Soy Foods
Dilated Cardiomyopathy
bisphenol A
Food Packaging
Endocrine Disruptors
Caspase 1
Pericarditis
Interleukin-17
Viral Genome
Pericardium
Gonadal Steroid Hormones
Interleukin-1

Keywords

  • bisphenol A
  • endocrine disruptor
  • estrogen receptor
  • mast cells
  • myocarditis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis. / Bruno, Katelyn Ann; Mathews, Jessica Elizabeth; Yang, Alex Lingyun; Frisancho, J. Augusto; Scott, Ashley Jennie; Greyner, Henry David; Molina, Frank Anthony; Greenaway, Merci Shekinah; Cooper, George Maxwell; Bucek, Adriana; Morales-Lara, Andrea Carolina; Hill, Anneliese Ruth; Mease, Anna Alisa; Di Florio, Damian Nicolas; Sousou, John Michael; Coronado, Alexandria Christine; Stafford, Allison Ray; Fairweather, De Lisa.

In: Frontiers in Endocrinology, Vol. 10, 598, 04.09.2019.

Research output: Contribution to journalArticle

Bruno, KA, Mathews, JE, Yang, AL, Frisancho, JA, Scott, AJ, Greyner, HD, Molina, FA, Greenaway, MS, Cooper, GM, Bucek, A, Morales-Lara, AC, Hill, AR, Mease, AA, Di Florio, DN, Sousou, JM, Coronado, AC, Stafford, AR & Fairweather, DL 2019, '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, vol. 10, 598. https://doi.org/10.3389/fendo.2019.00598
Bruno, Katelyn Ann ; Mathews, Jessica Elizabeth ; Yang, Alex Lingyun ; Frisancho, J. Augusto ; Scott, Ashley Jennie ; Greyner, Henry David ; Molina, Frank Anthony ; Greenaway, Merci Shekinah ; Cooper, George Maxwell ; Bucek, Adriana ; Morales-Lara, Andrea Carolina ; Hill, Anneliese Ruth ; Mease, Anna Alisa ; Di Florio, Damian Nicolas ; Sousou, John Michael ; Coronado, Alexandria Christine ; Stafford, Allison Ray ; Fairweather, De Lisa. / BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis. In: Frontiers in Endocrinology. 2019 ; Vol. 10.
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abstract = "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.",
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AU - Yang, Alex Lingyun

AU - Frisancho, J. Augusto

AU - Scott, Ashley Jennie

AU - Greyner, Henry David

AU - Molina, Frank Anthony

AU - Greenaway, Merci Shekinah

AU - Cooper, George Maxwell

AU - Bucek, Adriana

AU - Morales-Lara, Andrea Carolina

AU - Hill, Anneliese Ruth

AU - Mease, Anna Alisa

AU - Di Florio, Damian Nicolas

AU - Sousou, John Michael

AU - Coronado, Alexandria Christine

AU - Stafford, Allison Ray

AU - Fairweather, De Lisa

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N2 - 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.

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