Abstract
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.
Highlights
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
We selected a total of 16 anatomically defined regions from each heart for MS analysis (Fig. 1a, b): the atrial and ventricular septa (SepA and SepV) separating the atria and ventricles, respectively; the right atrium (RA) and right ventricle (RV) connected via the tricuspid valve (TV); the left atrium (LA) and left ventricle (LV) linked via the mitral valve (MV); the right and left ventricles connected to the pulmonary artery (PA) and aorta (Ao) via the pulmonary and aortic valves (PV and AV); the inferior vena cava (IVC) collecting deoxygenated blood; the pulmonary vein (PVe) carrying oxygenated blood; and the main right and left coronary arteries (RCA and left coronary artery (LCA)) supplying the heart with oxygen-rich blood
We found high correlation (0.92) in protein expression between the fibroblast cell types (CF and another fibroblast cell type (AFs)), whereas smooth muscle cells (SMCs) and endothelial cells (ECs) were somewhat less related (0.81) and this is reflected in the principal component analysis (PCA) (Supplementary Fig. 12 and Fig. 5b)
Summary
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. The human heart is composed of four major cell types—cardiac fibroblasts (CFs), cardiomyocytes, smooth muscle cells (SMCs), and endothelial cells (ECs)[1]. Their proportion with respect to number and volume, remains controversial. The high dynamic range of the muscle proteome presents a formidable challenge to the comprehensive analysis of the heart at the level of expressed proteins. This is because very abundant proteins make it difficult to detect low abundant regulatory proteins in the same sample. The majority of studies only identified a few thousand proteins, and there is a paucity of studies of the human, nondiseased heart, because of the difficulty in obtaining the relevant tissue
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