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Low-dose exposure to bisphenol A in combination with fructose increases expression of genes regulating angiogenesis and vascular tone in juvenile Fischer 344 rat cardiac tissue
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
University of California, Irvine, Department of Developmental and Cell Biology, Irvine, CA 92697, USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
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2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 20-27Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Epidemiological studies report associations between exposure to the high-volume chemical and endocrine disruptor bisphenol A (BPA) and cardiovascular disorders, but there is a lack of experimental studies addressing the mechanisms of action of BPA on the cardiovascular system. In the present study, effects on markers for cardiovascular function of exposure to BPA and fructose in vivo in rat cardiac tissues, and of BPA exposure in human cardiomyocytes in vitro, were investigated.

MATERIALS: Juvenile female Fischer 344 rats were exposed to 5, 50, and 500 μg BPA/kg bodyweight/day in their drinking water from 5 to 15 weeks of age, in combination with 5% fructose. Further, cultured human cardiomyocytes were exposed to 10 nM BPA to 1 × 10(4) nM BPA for six hours. Expression of markers for cardiovascular function and BPA target receptors was investigated using qRT-PCR.

RESULTS: Exposure to 5 μg BPA/kg bodyweight/day plus fructose increased mRNA expression of Vegf, Vegfr2, eNos, and Ace1 in rat heart. Exposure of human cardiomyocytes to 1 × 10(4) nM BPA increased mRNA expression of eNOS and ACE1, as well as IL-8 and NFκβ known to regulate inflammatory response.

CONCLUSIONS: . Low-dose exposure of juvenile rats to BPA and fructose induced up-regulation of expression of genes controlling angiogenesis and vascular tone in cardiac tissues. The observed effects of BPA in rat heart were in line with our present and previous studies of BPA in human endothelial cells and cardiomyocytes. These findings may aid in understanding the mechanisms of the association between BPA exposure and cardiovascular disorders reported in epidemiological studies.

Place, publisher, year, edition, pages
2017. Vol. 122, no 1, p. 20-27
Keyword [en]
Angiogenesis, bisphenol A, cardiomyocytes, cardiovascular disease, endocrine disruption, fructose, heart, vascular tone
National Category
Pharmacology and Toxicology General Practice
Identifiers
URN: urn:nbn:se:uu:diva-311874DOI: 10.1080/03009734.2016.1225870ISI: 000396476600003PubMedID: 27622962OAI: oai:DiVA.org:uu-311874DiVA, id: diva2:1061749
Funder
Swedish Research Council Formas, 216-2009-972
Available from: 2017-01-03 Created: 2017-01-03 Last updated: 2018-01-13Bibliographically approved

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Lejonklou, Margareta H.Rönn, MonikaLind, LarsLind, P. MonicaBrittebo, Eva
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