Matrix Metalloproteinases in Pathogenesis of Ventilation Disorders of the Respiratory System in Patients with Chronic Pulmonary Tuberculosis

Abstract

The imbalance in matrix metalloproteinase (MMP)/inhibitors system leads to degradation of extracellular matrix of connective tissue and pathological remodeling forming the morphological basis for respiratory dysfunction.The objective: to study the relationship between parameters of MMP/inhibitors system in blood and parameters of ventilation and gas exchange disorders in patients with chronic pulmonary tuberculosis (PTB).Subjects and Methods. Patients with the verified diagnosis of tuberculoma (n = 45) and fibrous-cavernous pulmonary tuberculosis (n = 85) were examined. All patients underwent computed tomography of the chest and assessment of respiratory function. Serum concentrations of MMP-1, -3, -8, -9 and their inhibitors TIMP-1 and α2-macroglobulin (MG) were tested by ELISA (R&D Systems, Minneapolis, MN, USA). Statistica 7.0 and an ANCOVA model were used for statistical analysis which considered the diagnosis and smoking status as factors, and the respiratory function parameters were considered as covariates.Results. In pulmonary tuberculosis patients, the concentrations of MMP-9 and MMP-8 in the blood correlated with extension of lung parenchyma lesions when compared to tuberculomas and fibro-cavernous tuberculosis, MMP-9 and TIMP-1 with changes in lung volumes (R2 = 0.60 and 0.80; p = 0.001), and MMP-8 correlated with functional disorders of gas exchange (R2 = 0.60 and 0.80; p = 0.001). Changes in MMP-1, MMP-3, and α2-MG (R2 = 0.60 and 0.80; p = 0.45) did not correlate with extension of lung parenchymal lesions and decreased lung function.