Association of matrix metalloproteinase 3 and endogenous inhibitors with inflammatory markers in mitral valve disease and calcification.

Abstract

Calcific mitral valve stenosis (MVS) is a common disease characterized by extensive remodeling of the extracellular matrix via matrix metalloproteinases (MMPs). The mechanism of calcification due to extensive matrix remodeling remains unclear. In this study, we investigated the relationship between MMP-3, tissue inhibitors of metalloproteinases (TIMPs) as well as pro-inflammatory cytokines and the phenomenon of calcification in MVS. 212 patients having rheumatic mitral stenosis (RMS) and 155 healthy control subjects were recruited in the Cardiology Department of La Rabta Hospital University. Levels of MMP-3, TIMPs, IL-6 and TNF-α were measured by ELISA sandwich assay, hs-CRP was measured by immunoturbidimetry. Plasma levels of MMP-3, TIMP-1 and MMP-3/TIMP-2 ratio were lower only in RMS women in comparison to the control group. Calcification degree correlated positively with MMP-3 in women and men. In addition, calcification was correlated positively with MMP-3/TIMPs ratio in women patients. The inflammatory parameters were positively associated with extracellular matrix turnover biomarkers in men patients. In patients, the level of MMP-3 was increased in men and women with a calcification score ≥ 5. In addition, MMP-3 level predicted the occurrence of calcification. At ROC curves analysis, the cut-off MMP-3 level was in women was 9.21ng/ml (sensitivity 51.1%, specificity 89.3%) and in men was 12.84ng/ml (sensitivity 78.6%, specificity 77.8%). The high levels of MMP-3 and the biomarkers of inflammation contribute to valvular remodeling and calcification of the mitral valve.