Human cardiac myosin light chain 4 (MYL4) mosaic expression patterns vary by sex
Human cardiac myosin light chain 4 (MYL4) mosaic expression patterns vary by sex
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DOI：
10.1038/s41598-019-49191-0
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发表时间：
2019-09-03
影响因子：
4.6
通讯作者：
Halushka, Marc K.
中科院分区：
文献类型：
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作者：
Wang, TonyY;Arking, Dan E.;Halushka, Marc K.
性别差异调节心脏功能，尽管其蛋白质和机制仍有待阐明。我们最近展示了心脏中100多种蛋白质的马赛克表达模式。在这里，我们研究了其中的一种蛋白质，肌球蛋白轻链4(MYL4)，它通过增加力量的产生而对收缩功能起重要作用。我们利用一种半自动细胞分析方法，分析了来自668个个体的756个心室心肌样本中MYL4的表达模式，这些组织微阵列(TMA)涵盖了不同的疾病。在所有五个TMA中，MYL4阳性细胞的百分比在男性受试者中显著较高，与疾病状态无关(p=8.66e-15)。MYL4的高表达也与肥厚型心肌病有一定的相关性(p=6.3e-04)。MYL4的表达与心脏性猝死或其他心肌病无关。这项研究展示了一种新的蛋白质表达马赛克模式，这种模式是人类心脏性别差异的基础。
Sex disparities modulate cardiac function, although the proteins and mechanisms remain to be elucidated. We recently demonstrated a mosaic pattern of protein expression in the heart for over 100 proteins. Here we investigate one of these proteins, myosin light chain 4 (MYL4), which is important for contractile functions by increasing force production. We assayed the expression pattern of MYL4 across 756 ventricular myocardial samples from 668 individuals utilizing a semi-automated Cell Profiler method on five tissue microarrays (TMAs) of cardiac tissues across a diverse set of diseases. The percentage of MYL4 positive cells was significantly higher in male subjects independently across all five TMAs, regardless of disease state (p = 8.66e-15). Higher MYL4 expression was also modestly associated with hypertrophic cardiomyopathy (p = 6.3e-04). MYL4 expression did not associate with sudden cardiac death or other cardiomyopathies. This study demonstrates a new mosaic pattern of protein expression that underlies sex disparities in the human heart.