Pathogenetic mechanisms of the association of MMP-9 and TIMP-1 biomarkers with the severity of chronic obstructive pulmonary disease

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Abstract

Background. Inflammation, oxidative stress, and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD).

Objective. Determination of the serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and evaluation of their association with the severity of COPD symptoms.

Methods. In a cohort study, serum MMP-9 and TIMP-1 levels, the ratio of MMP-9/TIMP-1 in the peripheral blood of COPD patients and in the control group, as well as their relationship with pulmonary function were determined. Spirometry, symptom severity scale (mMRC and CAT), and history of exacerbations were assessed.

Results. COPD patients (n=96) had significantly higher serum MMP-9 and TIMP-1 levels, higher MMP-9/TIMP-1 ratio than controls (n=40) (P ≤0.001). MMP-9 and MMP-9/TIMP-1 ratio were negatively correlated with FVC, FEV1, FEV1/FVC (P<0.05). COPD GOLD-3-4 patients had higher MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to COPD GOLD-1-2 patients (P≤0.001).

Conclusion. In patients with COPD, serum MMP-9 and TIMP-1 levels and the MMP-9/TIMP-1 ratio were elevated. In patients with COPD, there was an imbalance between MMP-9 and TIMP-1 in favor of fibrosis, which generally indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for the diagnosis and severity of COPD.

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About the authors

L. V. Vasilyeva

Voronezh State Medical University n.a. N.N. Burdenko

Email: suslova_ekaterina2502@mail.ru
ORCID iD: 0000-0002-9900-556X
Russian Federation, Voronezh

E. V. Gosteva

Voronezh State Medical University n.a. N.N. Burdenko

Email: suslova_ekaterina2502@mail.ru
ORCID iD: 0000-0002-8771-2558
Russian Federation, Voronezh

E. Yu. Suslova

Voronezh State Medical University n.a. N.N. Burdenko

Author for correspondence.
Email: suslova_ekaterina2502@mail.ru
ORCID iD: 0000-0002-5407-0384

Cand. Sci. (Med.), Associate Professor at the Department of Propaedeutics of Internal Diseases

Russian Federation, Voronezh

L. R. Elzhurkaeva

Kadyrov Chechen State University

Email: suslova_ekaterina2502@mail.ru
ORCID iD: 0000-0003-2445-6849
Russian Federation, Grozny

М. А. Zolotareva

Voronezh State Medical University n.a. N.N. Burdenko

Email: suslova_ekaterina2502@mail.ru
ORCID iD: 0000-0002-9491-086X
Russian Federation, Voronezh

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