Gordienko J. Expression and activity of matrix-degrading enzymes in cardiovascular and oncohematological diseases.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0415U005318

Applicant for

Specialization

  • 03.00.04 - Біохімія

08-09-2015

Specialized Academic Board

Д 26.001.24

Taras Shevchenko National University of Kyiv

Essay

The expression and activity of matrix-degrading enzymes in cardiovascular and oncohematological diseases is studied in the research work. The doxorubicin cardiomyopathy in rats was shown to be accompanied by morphological and biochemical changes such as spherical shape of heart, increased level of connective tissue component of myocardium, increased activity of aspartate aminotransferase, lactate dehydrogenase and increased levels of cholesterol and triglycerides in the blood plasma. Enhanced expression of matrix metalloproteinase 2 and 9 in cardiac muscle tissues of rats and increased the activity of these enzymes in the fraction of soluble proteins as well as in blood plasma was revealed. In addition, it was established that the activity of MMP9 increased at early stages of the disease, while MMP2 activity increased later on. It was discovered that changes in the activity studied enzymes under the application of the antioxidant drugs had diverse nature: corvitin decreased, where as alfa-ketoglutarate increased these parameters. The activity of trypsin-like enzymes increased in the blood plasma, however, decreased in heart muscle. Under the influence of corvitin and alfa-ketoglutarate, they were restored to physiological values. Proliferative blood diseases were accompanied by the significant changes in the activity of matrix metalloproteinases 2 and 9. It was established that under the treatment of anthracycline antibiotics activity of proMMP9 varied considerably. The activity of this enzyme was significantly reduced in acute myeloid leukemia (0,03 ± 0,01 rel. u.) and increased by 2,76 times in multiple myeloma before the chemotherapy compared to the control. The activity of proMMP9 in patients with acute myeloid leukemia increased 7-fold after the treatment comparatively to the indicators before the chemotherapy; in chronic lymphocytic leukemia it declined to 0,25 ± 0,06 rel. u. In multiple myeloma significant decrease of proMMP9 activity and considerable increase of MMP9 (0,17 ± 0.10 rel. u. and 1,46 ± 0,15 rel. u.) was observed.

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