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 9.21 ng/ml (sensitivity 51.1%, specificity 89.3%) and in men was 12.84 ng/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.
Subject(s)
Cardiomyopathies/metabolism , Matrix Metalloproteinase 3/metabolism , Matrix Metalloproteinase 3/physiology , Adult , Aged , Biomarkers/blood , C-Reactive Protein , Calcinosis/metabolism , Extracellular Matrix , Female , Humans , Inflammation , Interleukin-6 , Male , Matrix Metalloproteinase Inhibitors/metabolism , Middle Aged , Mitral Valve/metabolism , Mitral Valve Stenosis/metabolism , Mitral Valve Stenosis/pathology , Tissue Inhibitor of Metalloproteinase-1 , Tissue Inhibitor of Metalloproteinase-2 , Tissue Inhibitor of Metalloproteinases/metabolism , Tumor Necrosis Factor-alpha , Vascular Calcification/metabolismABSTRACT
BACKGROUND: The role of chronic inflammation in mitral restenosis after percutaneous mitral commissurotomy (PMC) is still controversial. AIMS: We sought to assess the predictive value of inflammation and extracellular matrix (ECM) remodeling biomarkers in late mitral restenosis after PMC. METHODS: We prospectively enrolled 155 patients (mean age 46.2±11 years) with at least 5 year follow up after primary PMC. Serum levels of high sensitive C-Reactive Protein (hs-CRP), matrix metalloproteinases MMPs, tissue-specific inhibitors of matrix metalloproteinases TIMPs, and tumor necrosis factor α (TNFα)] were measured. RESULTS: Late mitral restenosis occurred in 55 patients (35.5%). The independent predictors of late mitral stenosis were: age> 55 years [HR10.51 (95%CI 1.12-95.9); p=0.037]; no long acting penicillin therapy [HR 18.1 (95% CI 2.6-122.9); p=0.003]; TNFα > 80 ng/ml [HR 5.85 (95% CI 1.1-31.42); p=0.039]; and TIMP-2 > 289 ng/ml [HR 0.52 (95% CI 0.22-0.95); p=0.045]. CONCLUSION: Chronic inflammation and ECM remodeling are involved in late mitral restenosis after PMC.
Subject(s)
Biomarkers/metabolism , Cardiac Surgical Procedures/adverse effects , Extracellular Matrix/metabolism , Mitral Valve Stenosis/diagnosis , Mitral Valve Stenosis/surgery , Mitral Valve/surgery , Postoperative Complications , Adult , Aged , C-Reactive Protein/metabolism , Echocardiography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mitral Valve Stenosis/metabolism , Prospective Studies , Recurrence , Time Factors , Tissue Inhibitor of Metalloproteinase-2/metabolismABSTRACT
AIMS: This study investigates the relationships between matrix metalloproteinases, inflammations mediators and type 2 diabetes mellitus in Tunisians metabolic syndrome (Mets) patients. METHODS: The study has included 239 MetS patients and 247 controls. Mets was defined according to the NCEP-ATPIII report. Mets patients were also divided into two categories: 29 MetS non-diabetics and 210 MetS diabetics. Dysglycemia markers, matrix metalloproteinase-9 (MMP-9), Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), tumor necrosis factor α (TNF-α), C-reactive protein (CRP) levels and White Blood Cells (WBC) counts were determined in patients and controls. RESULTS: In our study, the level of inflammatory markers WBC, TNF-α and matrix metalloproteinases (MMP-8 and MMP-9) were significantly higher in diabetic patients with MetS, as compared with non-diabetic MetS patients. Inflammation mediators and MMP-9 were significantly associated with many clinical characteristics of MetS. The use of ROC "Receiver Operating Characteristic" analysis revealed the impact of TNF alpha on diabetes patients with MetS. In fact TNF alpha was found as a sensitive parameter in these patients with a sensitivity of 85%. CONCLUSION: Inflammation, matrix metalloproteinases and dysglycemia markers are not expressed in isolation but rather concurrently and are continuously interacting with each other, in MetS and diabetics patients. These markers fit with an early stage of cardiovascular disease (CVD); and measuring them could improve the risk evaluation, an early diagnosis, and the prognosis of CVD.
