School of Mathematics and Statistics, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Precision Cardiovascular Laboratory, The University of Sydney, Sydney, NSW, Australia.
Nat Commun. 2020 Jun 2;11(1):2843. doi: 10.1038/s41467-020-16584-z.
Poor access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a carefully procured large human heart biobank of cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide. We perform unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, compared to age-, gender-, and BMI-matched, histopathologically normal, donor controls. We report a dramatic reduction in serum amyloid A1 protein in ICM hearts, perturbed thyroid hormone signalling pathways and significant reductions in oxidoreductase co-factor riboflavin-5-monophosphate and glycolytic intermediate fructose-6-phosphate in both; unveil gender-specific changes in HF, including nitric oxide-related arginine metabolism, mitochondrial substrates, and X chromosome-linked protein and metabolite changes; and provide an interactive online application as a publicly-available resource.
获取人类左心室心肌的困难是心力衰竭 (HF) 研究的一个重大限制。在这里，我们利用精心收集的大量冷冻保存的左心室心肌人类心脏生物库，直接从分子水平深入了解缺血性心肌病 (ICM) 和扩张型心肌病 (DCM)，这是全球 HF 最常见的原因。我们对 44 例冷冻保存的人类 ICM 和 DCM 心脏的 51 个左心室 (LV) 样本进行了无偏、深度蛋白质组学和代谢组学分析，并与年龄、性别和 BMI 匹配、组织病理学正常的供体对照进行了比较。我们报告了 ICM 心脏中血清淀粉样蛋白 A1 蛋白的急剧减少，甲状腺激素信号通路受到干扰，氧化还原酶辅因子核黄素-5-单磷酸和两种物质中糖酵解中间产物果糖-6-磷酸的显著减少；揭示了 HF 中的性别特异性变化，包括与一氧化氮相关的精氨酸代谢、线粒体底物以及 X 染色体相关的蛋白质和代谢物变化；并提供了一个交互式在线应用程序作为公开资源。
