Perinatal inflammation induces sex-related differences in cardiovascular morbidities in mice.
Perinatal inflammation induces sex-related differences in cardiovascular morbidities in mice.
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DOI：
10.1152/ajpheart.00484.2017
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
M. Velten;K. Heyob;Loren E Wold;L. Rogers
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文献类型：
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作者：
M. Velten;K. Heyob;Loren E Wold;L. Rogers
心血管健康和疾病的性别差异已经确定，男性心血管事件的发生率较高，但女性更容易发生心律失常。不良的胎儿环境现在被认为是成年期心血管疾病发展的一个原因，但对不良胎儿环境反应的性别相关差异尚未得到广泛探讨。子宫内和出生后暴露于炎症的组合与早产或出生时或出生后早期具有临床并发症的婴儿高度相关。我们以前已经观察到心脏收缩缺陷和失调的Ca 2+处理蛋白在我们的模型母体脂多糖（LPS）和新生儿高氧暴露（LPS/O2）。本研究验证了暴露于围产期炎症后成人病理学存在性别相关差异的假设。使用压力-容积评估，男性暴露于LPS/O2有更明显的收缩缺陷比类似暴露的女性，但女性往往有较长的PR间隔。与生理盐水/室内空气对照相比，LPS/O2暴露后，两种性别的α-肌球蛋白重链和连接蛋白43均降低，而雌性动物的microRNA 208 a、microRNA 208 b和结蛋白表达异常增加。我们的研究支持了我们的假设，即早期生活中暴露于炎症导致心血管功能的性别依赖性缺陷。新&值得注意的是，心血管疾病的性别特异性差异已被认可，但其机制和起源尚未得到很好的理解。不利的母体环境会影响心脏发育和以后的心血管疾病。这项研究确定了与围产期炎症相关的心脏病的性别差异。
Sex-related differences in cardiovascular health and disease have been identified, with males having a higher incidence of cardiovascular events but females more likely to develop arrhythmias. Adverse fetal environments are now accepted as a cause for the development of cardiovascular diseases in adulthood, but sex-related differences in response to adverse fetal environments have not been extensively explored. The combination of both in utero and postnatal exposure to inflammation is highly relevant for the infant that is born preterm or has clinical complications at birth or in early postnatal life. We have previously observed cardiac contractile deficiencies and dysregulation of Ca2+-handling proteins in our model of maternal lipopolysaccharide (LPS) and neonatal hyperoxia exposures (LPS/O2). This investigation tested the hypothesis that there are sex-related differences in the adult pathologies after exposure to perinatal inflammation. Using pressure-volume assessments, males exposed to LPS/O2 had more pronounced contractile deficiencies than similarly exposed females, but females tended to have long PR intervals. While both sexes demonstrated decreases in α-myosin heavy chain and connexin 43 after LPS/O2 exposure compared with saline/room air controls, females indicated aberrant increases in microRNA 208a, microRNA 208b, and desmin expression. Our study supports our hypothesis that early life exposure to inflammation results in sex-dependent deficits in cardiovascular function. NEW & NOTEWORTHY Sex-specific differences in cardiovascular disease are recognized, but the mechanisms and origins are not well understood. Adverse maternal environments can influence cardiac development and later cardiovascular disease. This study identifies sex-dependent differences in cardiac disease associated with perinatal inflammation.