CORRECTION OF ENDOTHELIAL DYSFUNCTION WITH SULFAPORIN IN HYPERCHOLESTEROLEMIC RABBITS
Abstract
In animals with experimental hypercholesterolemia, depending on the time of survey, we observed activation of smooth muscle cells and macrophages, causing development of inflammation in the intima, as evidenced by high levels of C-reactive protein (CRP), endothelin-1, and homocysteine. The aim of the study was to investigate the molecular mechanisms of endothelial dysfunction in HCH and the possibility of their correction with sulfaporin. Material and methods of the study Experiments were conducted on 46 Chinchilla rabbits with an average weight of 2.5–3.0 kg, kept on a standard diet. The model of experimental HCH in animals was reproduced by orally administering cholesterol (CS) dissolved in sunflower oil in a ratio of 0.2 g per 1 kg of body weight daily for 3 months. The development of hypercholesterolemia was assessed by the increase in the level of totalcholesterol (TC), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), which were determined on a biochemical analyzer. Results of the study. In this case, a progressive increase in the homocysteine level was established: an increase of 1.72 (P < 0.01); 2.33 (P < 0.001) and 2.89 (P < 0.001) times, respectively, for the periods of cholesterol administration of 1, 2 and 3 months. Considering that hyperhomocysteinemia enhances the capture of LDL by endothelial cells, it was of interest to study the relationship between these indicators. The studies showed that with a cholesterol level in LDL of 2.38 ± 0.27 mmol / l, the homocysteine content is 3.46 ± 0.25 pg / ml. With a cholesterol level in LDL of 4.08 ± 0.10; 5.97 ± 0.09 and 6.48 ± 0.11 mmol/l, the homocysteine content increases to 5.96 ± 0.05; 8.07 ± 0.43 and 9.99 ± 0.17 pg/ml, respectively. Conclusions. Hypercholesterolemia is manifested by activation of smooth muscle cells and macrophages, causing the development of inflammation in the intima, which is confirmed by high levels of CRP, endothelin-1, homocysteine.
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