New research by a team of scientists at the University of Cincinnati (UC) shows that bisphenol A (BPA) may be harmful for the heart, particularly in women.

Results of several studies are being presented in Washington, D.C., at ENDO 09, the Endocrine Society’s annual meeting, June 10-13.

A research team lead by Scott Belcher, PhD, Hong Sheng Wang, PhD, and Jo El Schultz, PhD, in the department of pharmacology and cell biophysics, found that exposure to BPA and/or estrogen causes abnormal activity in hearts of female rats and mice.

In addition, these researchers found that estrogen receptors are responsible for this affect in heart muscle cells.

“There is broad exposure to bisphenol A, despite recognition that BPA can have harmful effects,” Belcher says. “We had reason to believe that harmful cardiovascular affects can be added to the list.”

BPA, an environmental pollutant with estrogen activity, is used to make hard, clear plastic and is common in many food product containers. It has been linked to neurological defects, diabetes and breast and prostate cancer.

Using live cultures of cells isolated from rat or mouse hearts, researchers briefly exposed the cardiac cells to BPA and/or estrogen. Both compounds caused striking changes in the activity of cardiac muscle cells from females but not males. Additional studies revealed that these cellular changes in activity caused improperly controlled beating in the female heart.

“Low doses of BPA markedly increased the frequency of arrhythmic events,” Belcher says. “The effect of BPA on these cardiac arrhythmias was amplified when exposed to estradiol, the major estrogen hormone in humans.”

The mechanism underlying this harmful effect was investigated using cellular imaging techniques.

“BPA and/or estrogen rapidly stimulated contraction by altering control of the concentrations of free calcium inside the heart cell but only in heart muscle cells from females, showing that these effects were sex-specific,” Belcher says. “BPA’s presence increased the frequency of calcium ‘sparks’ from the sarcoplasmic reticulum—the part of the cardiac muscle that stores and releases calcium ions—indicating spontaneous release or ‘leak’ that’s likely causing the heart arrhythmias and may have other harmful actions, especially following heart attack.”

Belcher and colleagues also investigated the nature of the mechanisms that mediated the responses of the cardiac muscle cells to estrogen and BPA.

“Pharmacological studies using selective estrogen receptor drugs and animal models lacking estrogen receptors were used to investigate the role of each estrogen receptor in mediating the rapid sex-specific function effects of E2 and BPA in cells,” he says. “Our findings suggest that estrogen has opposing actions in cardiac cells.

“In female cardiac muscle cells, the blocking or genetic removal of estrogen receptor beta completely blocked the contractile effects of BPA and estrogen, while in males, blockade of the effects of estrogen receptor alpha caused the male heart to become more ‘female-like’ and become responsive to estrogen and BPA.

“These studies have identified new and important potential cardiac risks associated with BPA exposure that may be especially important for women’s heart health,” he says.

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This study was funded by grants from the National Institutes of Health and the UC Center for Environmental Genetics.

Contact: Katie Pence
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University of Cincinnati Academic Health Center