Division of Cardiovascular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sci Rep. 2019 Sep 3;9(1):12681. doi: 10.1038/s41598-019-49191-0.
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.
性别差异调节心脏功能，尽管其相关蛋白和机制仍有待阐明。我们最近在心脏中发现了超过 100 种蛋白的镶嵌式表达模式。在这里，我们研究了其中一种蛋白——肌球蛋白轻链 4（MYL4），它通过增加力的产生对收缩功能很重要。我们利用 Cell Profiler 半自动方法，在五个心脏组织组织微阵列（TMA）上对来自 668 个人的 756 个心室心肌样本进行了 MYL4 表达模式分析，这些组织样本涵盖了一系列不同的疾病。无论疾病状态如何，男性受试者的 MYL4 阳性细胞百分比在所有五个 TMA 中均显著更高（p=8.66e-15）。MYL4 的高表达也与肥厚型心肌病（p=6.3e-04）呈弱相关。MYL4 的表达与心源性猝死或其他心肌病无关。这项研究表明，人类心脏中的性别差异存在一种新的蛋白表达镶嵌模式。
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