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Relationships between Circulating Matrix Metalloproteinases, Tissue Inhibitor TIMP-2, and Renal Function in Patients

Małgorzata Kobusiak-Prokopowicz1, Konrad Kaaz1, Dominik Marciniak2

  • 1Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland.

Kidney & Blood Pressure Research
|November 21, 2021
PubMed
Abstract

Insights

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are linked to heart function and kidney disease in myocarditis patients. Elevated MMPs and TIMP-2 indicate impaired cardiac remodeling and renal dysfunction.

Area of Science:

  • Cardiovascular Research
  • Nephrology
  • Biochemistry

Background:

  • Myocardial extracellular matrix (ECM) homeostasis relies on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
  • Imbalances in MMPs and TIMPs contribute to pathological ECM remodeling, driving cardiovascular and kidney diseases.

Purpose of the Study:

  • To investigate serum levels of MMP-2, MMP-3, and TIMP-2 in myocarditis patients.
  • To determine the relationship between these MMPs/TIMP-2 levels and cardiac function (ejection fraction, longitudinal deformation).
  • To assess the association of MMPs/TIMP-2 with renal function (eGFR, creatinine) and chronic kidney disease (CKD) in myocarditis.

Main Methods:

  • Included 45 myocarditis patients (11 with CKD) who underwent cardiac magnetic resonance (CMR).
  • Measured serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2.
  • Correlated biomarker levels with cardiac parameters and renal function markers.

Main Results:

  • Serum MMP-2, MMP-3, and TIMP-2 negatively correlated with ejection fraction.
  • MMP-3 levels correlated with longitudinal deformation.
  • MMP-2, MMP-3, and TIMP-2 negatively correlated with estimated glomerular filtration rate (eGFR).
  • Myocarditis patients with CKD exhibited higher MMP-2 and TIMP-2 levels.

Conclusions:

  • MMP-2, MMP-3, and TIMP-2 concentrations are associated with left-ventricular ejection fraction and myocardial deformation, highlighting their role in post-inflammatory cardiac remodeling.
  • Negative correlations between eGFR and MMPs/TIMP-2, and positive correlation between creatinine and MMP-3, suggest their involvement in renal dysfunction.
Keywords:
Chronic kidney diseaseMatrix metalloproteinasesMyocarditisTissue inhibitor of metalloproteinases

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