Disruption of neonatal cardiomyocyte physiology following exposure to bisphenol-a.
Disruption of neonatal cardiomyocyte physiology following exposure to bisphenol-a.
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DOI：
10.1038/s41598-018-25719-8
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发表时间：
2018-05-09
影响因子：
4.6
通讯作者：
Posnack NG
中科院分区：
文献类型：
--
作者：
Ramadan M;Sherman M;Jaimes R 3rd;Chaluvadi A;Swift L;Posnack NG
双酚化学品通常用于制造聚碳酸酯塑料、聚氯乙烯塑料、树脂和热敏打印应用。人类通过接触消费品和/或医疗器械而无意中暴露于双酚。最近的报告显示双酚a（BPA）暴露与不良心血管结局之间存在联系;尽管这些研究仅限于成人受试者和模型。由于发育中的心脏和成人心脏的心脏生理学显着不同，我们的目的是使用新生儿心肌细胞模型评估BPA暴露对心脏功能的影响。新生大鼠心室肌细胞进行了监测，以评估细胞活力，自发搏动率，搏动率变异性，和钙处理参数的存在下，控制或双酚补充的媒体。测试了一系列剂量，以模拟环境暴露（10−9-10− 8 M）、最大临床暴露（10− 5 M）和超生理暴露水平（10− 4 M）。急性BPA暴露改变了心肌细胞的功能，导致自发搏动率减慢和搏动率变异性增加。BPA暴露也损害了细胞内钙的处理，导致钙瞬变幅度降低，钙瞬变上升和持续时间延长。钙处理的改变也增加了交替和跳跃搏动的倾向。值得注意的是，BPA处理对钙处理的影响部分可逆。我们的数据表明，急性BPA暴露可能会沉淀对收缩性能和/或电交替的继发性不良影响，这两者都依赖于细胞内钙稳态。
Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium-handling parameters in the presence of control or bisphenol-supplemented media. A range of doses were tested to mimic environmental exposure (10−9–10−8M), maximum clinical exposure (10−5M), and supraphysiological exposure levels (10−4M). Acute BPA exposure altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability. BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes, prolonged calcium transient upstroke and duration time. Alterations in calcium handling also increased the propensity for alternans and skipped beats. Notably, the effect of BPA-treatment on calcium handling was partially reversible. Our data suggest that acute BPA exposure could precipitate secondary adverse effects on contractile performance and/or electrical alternans, both of which are dependent on intracellular calcium homeostasis.
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影响因子：
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