Proteomic Mapping of Atrial and Ventricular Protein Abundance in Patients with Aortic Valve Stenosis

Objectives: This study was aimed to detect novel biomarkers for prognostic purposes in patients with severe aortic valve stenosis (AVS) by high-resolution proteomic analysis. In patients with severe AVS, disease may progress rapidly, resulting in significant mortality and morbidity. However, they may benefit from timely interventions. To select these patients, novel disease-related biomarkers are needed.

Methods: We generated a global heavy isotope-labeled quantitation standard from pluripotent stem cell-derived atrial and ventricular cardiomyocytes by stable isotope labeling by amino acids in cell culture (SILAC) to profile the proteomes of formalin-fixed paraffin-embedded (FFPE) atrial and left ventricular myocardium from 30 adult patients with AVS by high-resolution mass spectrometry. To uncover disease related proteins, we compared our data to publish datasets from healthy and diseased hearts.

Result: In total, 3,370 proteins were quantified. Statistical analysis revealed significant upregulation of 64 proteins in atrial and 27 proteins in ventricular myocardium, respectively, including several known chamber-specific marker proteins. Atrial upregulation of proteins that belong to the interstitial compartment or contribute to endocrine function was observed. Differentially expressed proteins were assigned to functional pathways with disease relevance, such as downregulation of ventricular mitochondrial proteins and development of ventricular fibrosis. Finally, we were able to propose a set of high abundance proteins, such as LGALS3BP, TUBA4A, TINAGL1, and LAMA2, as well as SRL, FHL1, and ATP2A2, that likely plays a crucial role in AVS-related heart disease.

Conclusion: Our data provide a comprehensive insight into the proteome in left ventricular hypertrophy and identify candidate proteins as diagnostic biomarkers in AVS.