Abstract
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 × 104 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 × 104 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.
Highlights
A growing bulk of scientific evidence has raised concerns about the health effects of human exposure to the endocrine disruptor bisphenol A (BPA)
The results showed increased Vegf mRNA expression in rats exposed to 5 lg BPA/ kg bodyweight/day (P < .01), 50 lg BPA/kg bodyweight/day (P < .05), and 500 (P < .001) lg BPA/kg bodyweight/day compared to fructose controls; rats exposed to 5 lg BPA/kg bodyweight/day (P < .05) and 500 (P < .01) lg BPA/kg bodyweight/day showed increased Vegf mRNA expression compared to water controls (Figure 1(A))
Rats exposed to 5 lg BPA/kg bodyweight/day (P < .01), 50 lg BPA/kg bodyweight/day (P < .05), and 500 (P < .05) lg BPA/kg bodyweight/day showed increased Ace1 mRNA expression compared to fructose controls, and rats exposed to 5 lg BPA/kg bodyweight/ day showed increased Ace1 mRNA expression compared to water controls (P < .05) (Figure 1(C))
Summary
A growing bulk of scientific evidence has raised concerns about the health effects of human exposure to the endocrine disruptor bisphenol A (BPA). BPA is a key component in polycarbonate plastics and epoxy resins, which are widely used in the manufacturing of consumer products [1]. According to a systematic review of studies on BPA, human exposure to this hormone-disrupting contaminant is low but widespread [3]. Absorption from the oral cavity leads to much higher internal exposure of BPA than that absorbed from the gastrointestinal tract [4]. A review of more than 80 biomonitoring studies report that unconjugated and conjugated BPA is routinely detected in human biological samples, indicating that the general population is internally exposed to the unconjugated form of BPA [5]
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