Sex-specific cardiovascular responses to control or high fat diet feeding in C57bl/6 mice chronically exposed to bisphenol A

长期暴露于双酚 A 的 C57bl/6 小鼠对对照或高脂饮食喂养的性别特异性心血管反应

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作者:Bhavini B Patel, Mohamad Raad, Igal A Sebag, Lorraine E Chalifour

Abstract

The increased pericardial fat which often accompanies overall obesity is thought to alter cardiac structure/function and increase the risk for atrial fibrillation. We hypothesized that chronic exposure to bisphenol A (BPA) would induce pericardial fat, cardiac hypertrophy or arrhythmia. C57bl/6n dams were exposed to BPA (25 ng/ml drinking water) beginning on gestation day 11 and progeny continued on 2.5 ng BPA/ml drinking water. The progeny of control dams (VEH) and dams treated with diethylstilbestrol (DES, 1 μg/kg/day, gestation days 11⿿14) had tap water. After weaning progeny were fed either a control (CD) or high fat diet (HFD) for 3 months. Pericardial fat was present in CD-BPA and CD-DES and not CD-VEH mice, and was increased in all HFD mice. Catecholamine challenge revealed no differences in males, but BPA-exposed females had longer P-wave and QRS complex duration. Only CD-BPA and CD-DES females developed cardiac hypertrophy which was independent of increased blood pressure. Calcium homeostasis protein expression changes in HFD-BPA and HFD-DES mice predict reduced SERCA2 activity in males and increased SERCA2 activity in females. Thus, chronic BPA exposure induced pericardial fat in the absence of HFD, and female-specific changes in cardiac hypertrophy development and cardiac electrical conduction after a catecholamine challenge.

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