Molecular Biology Reports

, Volume 45, Issue 6, pp 2135–2143 | Cite as

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

  • Sonia Aloui
  • Wiem Zidi
  • Sana Ouali
  • Imen Guizani
  • Sameh Hadj-Taieb
  • Mohamed Sami Mourali
  • Moncef Feki
  • Monia Allal-ElasmiEmail author
Original Article


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.


Mitral valve stenosis Calcification Matrix metalloproteinases Inflammation 



We thank all the personnel of Biochemistry and Cardiology departments for their collaboration throughout this study.


The study was supported by a grant from the “Ministry of High Education, Scientific Research and Technologies of Tunisia”.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of Rabta Hospital and informed consent was obtained from all participants to this study. This work was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans.


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine of TunisUniversity of Tunis El ManarTunisTunisia
  2. 2.Department of CardiologyLa Rabta HospitalTunisTunisia
  3. 3.Faculty of Sciences of BizerteUniversity of CarthageTunisTunisia

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