Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, 82152, Germany.
Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
Nat Commun. 2017 Nov 13;8(1):1469. doi: 10.1038/s41467-017-01747-2.
The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major cardiac cell types by high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, we quantify over 10,700 proteins in this high dynamic range tissue. We combine copy numbers per cell with protein organellar assignments to build a model of the heart proteome at the subcellular level. Analysis of cardiac fibroblasts identifies cellular receptors as potential cell surface markers. Application of our heart map to atrial fibrillation reveals individually distinct mitochondrial dysfunctions. The heart map is available at maxqb.biochem.mpg.de as a resource for future analyses of normal heart function and disease.
心脏是人体的重要器官，其相关疾病是全球范围内导致死亡的主要原因，但我们对心脏组成蛋白的特性和数量仍知之甚少。在此，我们通过高分辨率质谱蛋白质组学方法，对 16 个解剖区域和三种主要的心脏细胞类型进行了测量，从而确定了健康人类心脏的蛋白质组。我们从低至微克级的样本量中，对这个高动态范围的组织中超过 10700 种蛋白质进行了定量分析。我们将每个细胞的拷贝数与蛋白细胞器分配相结合，构建了亚细胞水平的心脏蛋白质组模型。对心脏成纤维细胞的分析确定了细胞受体作为潜在的细胞表面标志物。我们将心脏图谱应用于心房颤动的研究中，揭示了个体独特的线粒体功能障碍。心脏图谱可在 maxqb.biochem.mpg.de 上获取，为未来分析正常心脏功能和疾病提供了资源。
