Matrix metalloproteinases and inflammatory mediators: Usefulness of these markers in the progression of mitral stenosis

Mitral stenosis (MS) is the most frequent disease among rheumatic valvular-pathologies. Matrix Metalloproteinases (MMPs) and their specific inhibitors (TIMPs) implication in MS is yet to be elucidated. We aim in our study to highlight MS matrix remodeling and to exhibit the implication of matrix and inflammatory marker MS and in its complication. Our study included 174 patients diagnosed with rheumatic MS (received mitral commissurotomy with a mitral surface less than 1.5 cm 2 ). We also recruited 101 healthy controls. Levels of MMPs (MMP-2-3-9), TIMPs (TIMP-1-2) and Interleukin-6 (IL-6) were measured by ELISA sandwich assay. MMP-2 and MMP-9 were significantly higher in patients than controls and correlated positively with inflammatory markers.Matrix markers combined analysis revealed strong association with MS [AUC = 0.867 (95% CI 0.762–0.971); P < 0.001]. This combination showed a strong implication as for MMP-2. MMP-3 elevated level was associated to the calcification degree (≥ 5) and to auricular fibrillation (AF) presence. After further adjustment for age, gender and treatment (long acting penicillin), MMP-3 showed an independent association to the degree of calcification (≥ 5) [OR = 1.3 (95% CI 1.11–1.50); P < 0.001] compared to low calcified valvular patients (calcification < 5). MMP-3 showed also an independent association to AF when adjusted for the same risk factors. However, Il-6 was independently associated to restenosis in MS patients [OR = 1.4 (95% CI 1.04–1.95); P = 0.04] even after adjustment. Inflammation induces matrix remodeling towards extracellular matrix degradation and these phenomena trigger MS and its progression in calcification, AF and restenosis. These markers could be use as predictors of the disease progression.