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IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION

https://doi.org/10.15372/SSMJ20180601

Abstract

The aim of the study is to perform an immunohistochemical analysis of the expression of the vascular endothelial growth factor receptor 2 (VEGFR2) in the myocardium of Wistar rats in doxorubicin-induced cardiomyopathy and the administration of betulonic acid amide as an agent with a polytarget effect in comparison with the severity of destructive processes in heart muscle cells. Material and methods. Wistar male rats (total 51 animals) were used in the work with isolated and combined administration of a single sublethal dose of doxorubicin (7 mg/kg) and course administration of betulonic acid amide at doses of 50 mg/kg/day and 100 mg/kg/day for 3 and 14 days. Immunohistochemical evaluation of VEGFR2 expression in the myocardium was carried out with the calculation of the index of VEGFR2-positive cardiomyocytes; the volume density of cardiomyocytes with lytic changes was estimated using stereological analysis. Results and discussion. A single administration of doxorubicin (at a dose of 7 mg/kg) caused destructive changes in cardiomyocytes and hemodynamic disorders in myocardium, which increased with the duration of the experiment (14 days). The complex of the revealed structural and metabolic lesions reflected the development of regenerative-plastic insufficiency of cardiomyocytes, which is the basis of cardiac insufficiency in anthracycline cardiomyopathy. Morphological changes in the myocardium with isolated administration of betulonic acid amide were largely determined by the dose used. At a dose of 100 mg/kg, myocardial changes were similar in severity with doxorubicin-induced changes. Combined use of doxorubicin and betulonic acid amide revealed the most significant structural damage of the myocardium. It was shown that the increase in the volume density of lytic altered cardiomyocytes correlated with a significant increase in VEGFR2 expression (correlation coefficient varied from 0.620 to 0.980).

About the Authors

L. L. Elena
Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine
Russian Federation


M. M. Mzhelskaya
Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine
Russian Federation


E. V. Koldysheva
Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine
Russian Federation


M. G. Klinnikova
Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine
Russian Federation


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