Matrix metalloproteinases as a possible factor of biological prosthetic

Aim. To identify the expression and possible sources of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in bioprosthetic heart valves (BHVs).

Methods. The material for the study was epoxy-treated BHVs (NeoKor Ltd, Kemerovo) obtained during valve re-prosthetics. Cellular infiltration and ECM degradation were assessed by haematoxylin and eosin staining while lipid deposition and calcification were analysed by Oil Red O and Alizarin Red S staining. Сellular typing and detection of MMP-1/-2/-8/-9/-12 and TIMP-1/-2 expression in samples were performed using immunohistochemical staining with antibodies to CD45, CD68, СD3, CD19, myeloperoxidase, and to the corresponding MMPs and TIMPs. Analysis of samples was performed by light microscopy.

Results. We examined 7 xenoaortic and 7 xenopericardial BHVs which were removed during re-replacement from the aortic (n = 2) and mitral (n = 12) positions. In studied leaflets from 13 explanted BHVs, sporadic infiltrates consisting of macrophages and neutrophils were revealed. Semi-quantitative analysis showed that more aggressive cellular infiltration is characteristic of xenoaortic BHVs (p = 0.038). MMP-1/-2/-8/-12 and TIMP-1/-2 were weakly expressed and co-localised with infiltrating cells whilst MMP-9 was abundant in the loosened extracellular matrix (ECM) devoid of host cells.

Conclusion. The recipient cells infiltrating BHVs are sources of MMP-1/-2/-8/-9/-12 and TIMP-1/-2. In addition, MMP-9 can diffuse into BHVs leaflets from the blood of patients. 

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