Abstract
Aortic valve stenosis (AVS) is one of the most common valve diseases in the world. However, detailed biological understanding of the myocardial changes in AVS hearts on the proteome level is still lacking. Proteomic studies using high-resolution mass spectrometry of formalin-fixed and paraffin-embedded (FFPE) human myocardial tissue of AVS-patients are very rare due to methodical issues. To overcome these issues this study used high resolution mass spectrometry in combination with a stem cell-derived cardiac specific protein quantification-standard to profile the proteomes of 17 atrial and 29 left ventricular myocardial FFPE human myocardial tissue samples from AVS-patients. In our proteomic analysis we quantified a median of 1980 (range 1495–2281) proteins in every single sample and identified significant upregulation of 239 proteins in atrial and 54 proteins in ventricular myocardium. We compared the proteins with published data. Well studied proteins reflect disease-related changes in AVS, such as cardiac hypertrophy, development of fibrosis, impairment of mitochondria and downregulated blood supply. In summary, we provide both a workflow for quantitative proteomics of human FFPE heart tissue and a comprehensive proteomic resource for AVS induced changes in the human myocardium.
Highlights
Aortic valve stenosis (AVS) is one of the most common valve diseases in the world
When AVS patients develop the typical clinical symptoms, i.e., the triad of heart failure, angina, and s yncope[3] together with left ventricular dysfunction they are in urgent need for surgical or interventional aortic valve replacement (AVR)
A more detailed biological and molecular understanding of the changes that lead to myocardial decompensation and fibrosis, and biomarkers are needed for better risk stratification and to select patients that will benefit from urgent or earlier surgical treatment[3,9]
Summary
Aortic valve stenosis (AVS) is one of the most common valve diseases in the world. detailed biological understanding of the myocardial changes in AVS hearts on the proteome level is still lacking. Proteomic studies using high-resolution mass spectrometry of formalin-fixed and paraffin-embedded (FFPE) human myocardial tissue of AVS-patients are very rare due to methodical issues. Well studied proteins reflect disease-related changes in AVS, such as cardiac hypertrophy, development of fibrosis, impairment of mitochondria and downregulated blood supply. Abbreviations ABC Ammonium bicarbonate AVS Aortic valve stenosis CABG Coronary artery Bypass graft CMs Cardiomyocytes DCA Deoxycholic acid ECM Extracellular matrix FASP Filter-aided-sample preparation FFPE Formalin-fixed and paraffin-embedded GSEA Gene set enrichment analyses GO Gene ontology. When AVS patients develop the typical clinical symptoms, i.e., the triad of heart failure, angina, and s yncope[3] together with left ventricular dysfunction they are in urgent need for surgical or interventional aortic valve replacement (AVR). A more detailed biological and molecular understanding of the changes that lead to myocardial decompensation and fibrosis, and biomarkers are needed for better risk stratification and to select patients that will benefit from urgent or earlier surgical treatment[3,9]
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