Lobov, A., et al. “Proteomic profiling reveals unique signatures of structural bioprosthetic valve deterioration.” Atherosclerosis 355 (2022): 41-42. https://doi.org/10.1016/j.atherosclerosis.2022.06.349
Background and Aims : Half of the bioprosthetic heart valves (BHVs) demand a repeated replacement within 15 years postimplantation because of structural valve deterioration (SVD). The pathogenesis of SVD is far from being fully understood, largely due to the lack of high-throughput investigation of failed BHVs.
Methods: Failed bovine xenopericardial (XPB-BHVs, n = 5)) and porcine xenoaortic (XPA-BHVs, n = 5) BHVs and dysfunctional AVs (n = 5) were excised during the heart valve replacement. Label-free proteomic profiling was performed by means of liquid chromatography-tandem mass spectrometry with ion mobility (TimsToF Pro). Bioinformatic analysis was conducted using PEAKS Studio Xpro and R software environment. Proteins identified with false discovery rate < 1% and having ≥ 2 unique peptides were included into further analysis.
Results: Out of 1,614 protein groups identified, 73 were unique for BHVs and 70 proteins were overexpressed in BHVs. Of these 143 protein groups, 73 belonged to five major categories: complement components (17), neutrophil markers (19), proteases (7), platelet markers and coagulation factors (18), and lipid metabolism-related proteins (12). Matrix metalloproteinases (MMP-8 and MMP-9) were documented in BHVs but not in AVs, whereas their tissue inhibitors (TIMP-1 and TIMP-2) were upregulated in AVs, together indicative of unbalanced proteolysis in the failing BHVs. Presumably, loosening and disintegration of prosthetic matrix upon the constant haemodynamic stress provoke excessive lipid deposition, coagulation, microthrombosis, and inflammation.