Expression of cysteine cathepsins B/K/L/S/V/Z in failed bioprosthetic heart valves

Abstract

Background. Bioprosthetic heart valves (BHVs) are prone to the proteolytic degradation, eventually resulting in their degeneration and failure. Previously, we found cysteine cathepsins with a collagenase and elastase activity in bioprosthetic tissue but it remained unclear whether they precipitated from the circulating blood or have been produced by the infiltrating host cells.Aim: To study the distribution of cathepsin B, cathepsin K, cathepsin L, cathepsin S, cathepsin V, and cathepsin Z in bioprosthetic heart valves and to identify their source.Material and Methods. We examined five BHVs excised from the mitral position during the repeated heart valve replacement. Average duration of BHV functioning was 169 ± 31 months. Consecutive sections from the degenerated BHV segments were investigated by Russell-Movat’s pentachrome staining and immunohistochemistry, employing antibodies to leukocyte markers (pan-leukocyte marker CD45, macrophage marker CD68, neutrophil marker myeloperoxidase, T cell marker CD3, and B cell marker CD19) and cathepsins (B, K, L, S, V, and Z).Results. Macrocalcification and tears were the most frequent degenerative alterations found in BHV leaflets. Further, BHVs were notable for the fragmentation of collagen fibers at and beneath the surface, and were devoid of elastic fibers and mucopolysaccharides. Macrophages were co-localised with the degraded extracellular matrix foci. Cathepsin B was detected only in macrophages whilst other cathepsins (K, L, S, V, and Z) were expressed both in the immune cells and extracellular matrix.Conclusion. Macrophages are capable of producing all cysteine cathepsins in BHV leaflets. Localisation of cathepsins K, L, S, V, and Z in the extracellular matrix also indicated blood as their major source.