Dielievska V. Factors of fibrosis and degradation of extracellular matrix in chronic heart failure progression in patients with chronic obstructive pulmonary disease and arterial hypertension

Dissertation is devoted to the optimization of the diagnosis and treatment of patients with chronic heart failure (CHF) in arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD) based on the determination of the activity of the factors of fibrosis and extracellular matrix (ECM) degradation and their dynamics after the treatment. The main group included 80 patients with CHF II A stage II-III functional classes at AH of stage II and COPD of II-III degrees of bronchial obstruction and the comparison group consisted of 25 patients without COPD. The study showed that the course of CHF on the background of AH combined with COPD is accompanied by ECM changes, which is characterized by increased serum glycoproteins, chondroitinsulfates and chondroitin-6-sulfates and reduced hondroitin-4-sulfates / dermatansulfates. In patients with CHF at AH and COPD compared to patients without COPD we observed increased serum levels of matrix metalloprotease 9 (MMP-9), transforming growth factor ?1 (TGF-?1) and aldosterone, which were associated with left ventricular hypertrophy, however the development of the eccentric type of left ventricle myocardial hypertrophy, increased sizes of the right heart and the development of pulmonary hypertension were associated with increased levels of antibodies to type IV collagen. Progression of CHF in patients with AH and COPD was characterized by the weakening of the mechanisms of antiprotease protection and increased activity of autoimmune processes, as evidenced by decreased levels of ?2-macroglobulin and increased levels of antibodies to type IV collagen. The deterioration of the lung function in patients with AH and COPD was accompanied by increased levels of antibodies to type IV collagen and MMP-9 and an imbalance in the glycosaminoglycans metabolism evidenced by increased chondroitin-6-sulfates and reduced heparansulfates / keratansulfates. Use of spironolactone in addition to standard treatment in patients with CHF in AH and COPD improves lung function, reduces left ventricle hypertrophy and improves its diastolic function by lowering the levels of TGF-?1, aldosterone, MMP-9 and antibodies to type IV collagen as well as ECM components redistribution towards the decreased levels of glycoproteins, сhondroitinsulfates, chondroitin-6-sulfates and increased levels of heparansulfates / keratansulfates.