Cellular and Molecular Profiling of Native Heart Valves in Infective Endocarditis: A Comparative Study with Calcific Aortic Valve Disease.

Background: Infective endocarditis (IE) affects both native and prosthetic heart valves, the endocardial surface, as well as cardiac implantable electronic devices. Identifying specific IE biomarkers for its early risk stratification remains crucial, particularly in cases with blood culture-negative endocarditis. Methods: Eleven native heart valves obtained from IE and calcific aortic valve disease (CAVD) patients were analyzed. Immunohistochemical analysis of a pan-leukocyte marker (CD45), macrophage marker (CD68), T-lymphocyte marker (CD3), B-lymphocyte marker (CD19), neutrophil myeloperoxidase (MPO), and marker of vascular endothelial cells (CD31) was performed. Differentially expressed genes (DEGs) were identified by whole-transcriptome sequencing; proteomic profiling was performed by dot-blotting. Results: The immunophenotyping demonstrates the infiltration of macrophages and neutrophils, as well as occasional T-lymphocytes in the IE-affected aortic valves, and the CAVD-affected heart valves were characterized by the absence of neutrophils. For the whole-transcriptome sequencing, 157 DEGs were identified: 124 DEGs were upregulated, and 33 genes were downregulated in the IE-affected heart valves compared to the CAVD-affected ones. According to the dot-blotting, 35 cytokines were identified in the studied heart valves, but only 21 molecules were expressed in both IE and CAVD-affected heart valves. Analysis of proteases and their inhibitors allowed the identification of 13 protease molecules and 18 enzyme inhibitor molecules in all examined heart valves. Conclusions: The results of the present study can help to improve our understanding of the IE pathogenesis. In addition, we identified the candidate cellular and molecular-genetic features of IE-affected native heart valves.