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PROTEOLYTIC ACTIVITY IN THE HEART OF RATS WITH HYPERHOMOCYSTEINEMIA
Nataliia Raksha1, Oleksandr Maievskyi1, Iryna Dzevulska2
1TARAS SHEVCHENKO NATIONAL UNIVERSITY OF KYIV, KYIV, UKRAINE.
Insights
Hyperhomocysteinemia increases heart proteolytic activity and alters enzyme distribution. It also causes mild inflammation, indicated by elevated pro-inflammatory cytokines in young and old rats.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Immunology
Background:
- Hyperhomocysteinemia is a risk factor for cardiovascular disease.
- Proteolytic activity and cytokine profiles in the heart are crucial for cardiac function.
- Understanding these changes in hyperhomocysteinemia is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the distribution of proteolytic activity in the rat heart.
- To analyze the cytokine profile in rats with induced hyperhomocysteinemia.
- To correlate these changes with age in the context of hyperhomocysteinemia.
Main Methods:
- Induced hyperhomocysteinemia in 60 male rats using DL-homocysteine thiolactone.
- Measured total proteolytic activity using casein substrate.
- Assessed enzyme activity (metal-dependent and serine proteases) and cytokine levels (including MMPs and TIMP-1) via ELISA.
Main Results:
- Total proteolytic activity increased in the hearts of young, adult, and old rats.
- A shift towards metal-dependent proteases and away from serine proteases was observed, particularly in older animals.
- Mild inflammation, marked by increased pro-inflammatory cytokines, was present in young and old rats with hyperhomocysteinemia.
Conclusions:
- Hyperhomocysteinemia significantly alters cardiac proteolytic activity.
- Changes in the heart's cytokine profile accompany the pathogenesis of hyperhomocysteinemia.
- Age influences the response of proteolytic enzymes to hyperhomocysteinemia.
Objective:
The aim: To investigate the distribution of proteolytic activity and cytokine profile in the heart of rats with hyperhomocysteinemia.
Patients And Methods:
Materials and methods: A total of 60 albino non-linear male rats was used in the study. Hyperhomocysteinemia was induced by intragastric administration of DL-homocysteine thiolactone. Total proteolytic activity was measured using casein as a substrate. To determine the activity of metal-dependent and serine proteases, ethylenediaminetetraacetic acid, and phenylmethylsulfonyl fluoride were used. The level of matrix metalloproteinases, tissue inhibitor of metalloproteinases-1, and cytokines was studied by enzyme-linked immunosorbent assay.
Results:
Results: It was found an increase in the total proteolytic activity in the heart of young, adult, and old animals. In addition, the redistribution of proteolytic activity was revealed - the portion of metal-dependent enzymes increased in all groups while the percentage of serine proteases decreased in the old animals with hyperhomocysteinemia. The state of mild inflammation, evidenced by the increased level of some pro-inflammatory cytokines, was found in the heart of young and old animals with hyperhomocysteinemia.
Conclusion:
Conclusions: The pathogenesis of hyperhomocysteinemia is accompanied by a change in the proteolytic activity in the heart as well as a change in the cytokine profile.
