Multi-Omics Profiling of Hypertrophic Cardiomyopathy Reveals Altered Mechanisms in Mitochondrial Dynamics and Excitation-Contraction Coupling.
Multi-Omics Profiling of Hypertrophic Cardiomyopathy Reveals Altered Mechanisms in Mitochondrial Dynamics and Excitation-Contraction Coupling.
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肥厚性心肌病的多词分析揭示了线粒体动力学和激发诱导偶联的机制改变。
DOI：
10.3390/ijms24054724
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发表时间：
2023-03-01
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
肥厚型心肌病是最常见的遗传性心肌病之一，也是年轻人心脏性猝死的主要原因。尽管对遗传学有深刻的见解，但突变和临床预后之间的相关性并不完美，这表明复杂的分子级联驱动发病机制。为了研究这一点，我们进行了一个综合的定量多组学（蛋白质组学，磷酸蛋白质组学和代谢组学）分析，以阐明早期和直接的后果，在肌球蛋白重链突变的工程改造的人诱导多能干细胞衍生的心肌细胞相对于晚期疾病使用患者肌切除术。我们捕获了数百个差异特征，这些特征映射到在病理生物学的最早阶段调节线粒体稳态的不同分子机制，以及特定阶段的代谢和兴奋偶联适应不良。总的来说，这项研究填补了以前研究的空白，扩大了对突变的初始反应的了解，这些突变保护细胞免受收缩功能障碍和明显疾病之前的早期压力。
Hypertrophic cardiomyopathy is one of the most common inherited cardiomyopathies and a leading cause of sudden cardiac death in young adults. Despite profound insights into the genetics, there is imperfect correlation between mutation and clinical prognosis, suggesting complex molecular cascades driving pathogenesis. To investigate this, we performed an integrated quantitative multi-omics (proteomic, phosphoproteomic, and metabolomic) analysis to illuminate the early and direct consequences of mutations in myosin heavy chain in engineered human induced pluripotent stem-cell-derived cardiomyocytes relative to late-stage disease using patient myectomies. We captured hundreds of differential features, which map to distinct molecular mechanisms modulating mitochondrial homeostasis at the earliest stages of pathobiology, as well as stage-specific metabolic and excitation-coupling maladaptation. Collectively, this study fills in gaps from previous studies by expanding knowledge of the initial responses to mutations that protect cells against the early stress prior to contractile dysfunction and overt disease.
多构代谢富集网络分析揭示了癌症改变的代谢物蛋白质相互作用子网。
DOI：
10.1016/j.mcpro.2021.100189
发表时间：
2022-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Blum BC;Lin W;Lawton ML;Liu Q;Kwan J;Turcinovic I;Hekman R;Hu P;Emili A
通讯作者：
Emili A
影响因子：
5.6
作者：
Moore J;Emili A
通讯作者：
Emili A