Region and cell-type resolved quantitative proteomic map of the human heart and its application to atrial fibrillation

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 quantified over 11,000 proteins in this high dynamic range tissue. We combined copy numbers per cell with protein organellar assignments to build a model of the heart proteome at the subcellular level. Analysis of cardiac fibroblasts identified 25 cellular receptors as potential new cell surface markers. Application of our heart map to an atrial fibrillation study revealed signatures of 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.