Changes in the expression of the MADD gene in experimental models of myocardial hypertrophy

Abstract

Objective. The aim of the work was to evaluate the expression of the MADD gene during the development of myocardial hypertrophy caused by hemodynamic factors in the model of aortic coarctation, as well as in the model of renovascular arterial hypertension (model “2 kidney — 1 clip”). Design and methods. The study involved Wistar rats (n = 60) at the age of 8 weeks. Two experimental models of myocardial hypertrophy were used: the aortic coarctation model (n = 30) and the “2 kidneys — 1 clip” model (n = 21). Animals were divided into groups according to the duration of the experiment (1 and 10 weeks), we also formed a group of intact animals (n = 9). Myocardial hypertrophy was verified by echocardiography. After euthanasia and myocardial extraction, the tissues were homogenized in Extract RNA reagent (Evrogen) in order to obtain RNA. A complementary DNA strand was obtained by reverse transcription using Random (dN) 10-primer (Evrogen) and MMLV RT kit (Evrogen) primers. The relative expression level of the MADD gene in rat myocardium was determined using real-time polymerase chain reaction. The expression level was calculated using the ΔΔCt method; the GAPDH and HPRT genes were used as a reference control. Results. In the aortic coarctation model, MADD gene expression in the 1-week group was significantly higher (p < 0,05) compared with the intact group. In this model, there as a direct correlation of the expression of the MADD gene with NPPA gene, as well as with echocardiography indicators (final systolic size, final diastolic size, and myocardial mass index, p < 0,05), and an inverse relationship between MADD gene expression and the shortening fraction (p < 0,05). The renovascular hypertension model did not show a significant increase in the expression of the MADD gene in myocardium in experimental group compared to intact animals. Conclusions. The expression of the MADD gene increases mainly under the influence of acute hemodynamic overload, and is likely to be important for the immediate response by cardiomyocytes to pressure load. Correlation was found between the expression level of the MADD gene and such echocardiographic parameters as the shortening fraction, end-diastolic and end-systolic sizes of the left ventricle.