Comparative proteomic analysis of bioprosthetic heart valve explants due to structural valve deterioration

Y. Kang¹, J. Kim¹, S. Sohn², J. Choi¹, H. Hwang¹, K. Kim^1
1Seoul National University Hospital, SEOUL, Seoul-t'ukpyolsi ²Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Seoul-t'ukpyolsi

Purpose: Molecular mechanism of structural valve deterioration (SVD) has not yet been elucidated. Porcine valves are associated with cusp tears and valve incompetence, whereas bovine valves show gradual failure with stenosis. In this study, we identified candidate proteins and biological signatures associated with SVD using comparative proteomic analysis.

Methods: Label-free quantitative proteomics on freshly frozen explants due to severe SVD from June 2021 to February 2022 (N=11; Bovine: 7, Porcine: 4) was performed. Protein was extracted after sonication, and acetone protein precipitation was performed. Subsequently, on-pellet in-solution digestion was carried out, followed by liquid chromatography with tandem mass spectrometry. Log2 transformation, quartile normalization, and analysis of variance (ANOVA) were conducted. Hierarchical clustering of each differentially expressed protein (DEP) was performed, and a principal component analysis plot and heatmap showing expression patterns were generated. Gene ontology analysis was conducted to characterize the functional interpretation of proteomic data.

Results: The ANOVA analysis resulted in 71 differentially expressed proteins (DEPs). Bovine pericardial valves were associated with DEPs related to small molecule metabolic processes, response to abiotic stimuli, and generation of precursor metabolites and energy. Porcine valves were associated with immune response, carboxylic acid metabolism, and metabolic processes.

Conclusion: We report the first study that performed comparative proteomics on bioprosthetic valve explant samples to identify novel diagnostic biomarkers for SVD patients. Our results revealed increased levels of proteins related to the immune response in porcine explants compared to the bovine explants.

Identify the source of the funding for this research project: None