Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics
Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics
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DOI：
10.1152/ajpheart.00634.2016
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发表时间：
2017-03-01
影响因子：
4.8
通讯作者：
Hollander, John M.
中科院分区：
文献类型：
--
作者：
Hathaway, Quincy A.;Nichols, Cody E.;Hollander, John M.
随着新的工业和消费应用的引入，纳米材料的生产正在扩大。然而，接触这些化合物的影响尚未完全实现。本研究旨在确定妊娠期纳米二氧化钛暴露是否影响发育中后代的心脏和代谢功能。怀孕的Sprague-Dawley大鼠从妊娠第5-6天开始，非连续7-8天暴露于纳米气溶胶（类似于10 mg/m3，130- 150 nm计数中位空气动力学直径）。在三个时间点，胎儿（妊娠第20天），新生儿（4-10天），和年轻的成年人（6-12周），对心脏功能和心肌细胞的生理和生物能量的影响进行了评价。利用超声心动图，斑点跟踪应变，心肌细胞收缩力，再加上线粒体能量学的功能分析，揭示了纳米曝光的影响。母体暴露的后代表现出E波和A波速度的降低，E/A比值比对照组高15%。从暴露动物中分离的肌细胞显示出总收缩力、离开速度和收缩面积降低30%。生物能量分析显示，在所有年龄段的质子泄漏显着增加，伴随着代谢功能，包括基础呼吸，最大呼吸，和备用容量的下降。最后，电子传递链复合物I和IV的活动在暴露组中受到负面影响，这可能与代谢转变有关。分子数据表明，脂肪酸代谢，解偶联和细胞应激蛋白的增加可能与心脏功能缺陷有关。总之，妊娠期纳米暴露通过心肌细胞损伤显著损害心脏的功能能力，心肌细胞损伤与线粒体功能障碍有关。新&值得注意的是，首次在母体吸入纳米材料后的后代中评估心脏功能。研究结果表明，妊娠期间暴露于纳米二氧化钛（nanoTiO（2））会对心脏功能和线粒体呼吸以及生物能量学产生负面影响。我们的结论是，母亲吸入纳米二氧化钛有助于不良心血管健康影响，持续到成年。
Nanomaterial production is expanding as new industrial and consumer applications are introduced. Nevertheless, the impacts of exposure to these compounds are not fully realized. The present study was designed to determine whether gestational nanosized titanium dioxide exposure impacts cardiac and metabolic function of developing progeny. Pregnant Sprague-Dawley rats were exposed to nano-aerosols (similar to 10 mg/m(3), 130-to 150-nm count median aerodynamic diameter) for 7-8 nonconsecutive days, beginning at gestational day 5-6. Physiological and bioenergetic effects on heart function and cardiomyocytes across three time points, fetal (gestational day 20), neonatal (4-10 days), and young adult (6-12 wk), were evaluated. Functional analysis utilizing echocardiography, speckle-tracking based strain, and cardiomyocyte contractility, coupled with mitochondrial energetics, revealed effects of nano-exposure. Maternal exposed progeny demonstrated a decrease in E-and A-wave velocities, with a 15% higher E-to-A ratio than controls. Myocytes isolated from exposed animals exhibited similar to 30% decrease in total contractility, departure velocity, and area of contraction. Bioenergetic analysis revealed a significant increase in proton leak across all ages, accompanied by decreases in metabolic function, including basal respiration, maximal respiration, and spare capacity. Finally, electron transport chain complex I and IV activities were negatively impacted in the exposed group, which may be linked to a metabolic shift. Molecular data suggest that an increase in fatty acid metabolism, uncoupling, and cellular stress proteins may be associated with functional deficits of the heart. In conclusion, gestational nano-exposure significantly impairs the functional capabilities of the heart through cardiomyocyte impairment, which is associated with mitochondrial dysfunction.NEW & NOTEWORTHY Cardiac function is evaluated, for the first time, in progeny following maternal nanomaterial inhalation. The findings indicate that exposure to nano-sized titanium dioxide (nanoTiO(2)) during gestation negatively impacts cardiac function and mitochondrial respiration and bioenergetics. We conclude that maternal nano-TiO2 inhalation contributes to adverse cardiovascular health effects, lasting into adulthood.