The evaluation of expression of receptor and regulatory proteins genes in the myocardium of rats with chronic heart failure

Abstract

The purpose. The purpose of the study is to assess the level of expression of receptor and regulatory proteins genes involved in remodeling and myocardial contractility in rats with chronic heart failure. Methods. A complex of echocardiographic and molecular biological research methods was used. Gene expression was assessed by the level of mRNA in tissue samples of the left ventricle of rats extracted on day 92 after the coronary artery ligation (CHF group) or summation of the ligature under the coronary artery (sham-operated group). RNA isolation from the left ventricular tissue of the heart was performed using the GeneJETТМ kit, cDNA synthesis using the RevertAid™ H Minus First Strand cDNA Synthesis Kit (Thermo Fisher Scientific, USA), PCR-RV was performed using the qPCRmix-HS kit (Evrogen, Russia), using primers and fluorescent probes (DNA synthesis, Russia), according to manufacturers protocols. Results. It has been established that chronic heart failure (CHF) is formed 90 days after the reproduction of anterior transmural myocardial infarction, as evidenced by a decrease in heart pumping function and an increase in the end-systolic and end-diastolic sizes of the heart left ventricle. It is shown that CHF increases the expression of genes involved in myocardial remodeling. Thus, in left ventricular biopsy samples of rats with CHF, the level of mRNA for angiotensin receptors of AT1A type increases by 41% (p = 0.006), by 33% (p = 0.01) for vasopressin V1A-R and by 71% (p = 0.01) for endothelin ETA-R compared with similar indicators in sham-operated animals. In rats with CHF, the β₁-AR and β₂-AR mRNA levels in the left ventricle exceeded that in the sham-operated animals, respectively, by 35% (p = 0.001) and 48% (p = 0.0001). A high level of gene expression of the Epac2 and CaM proteins, which play a key role in arrhythmogenesis, is evidenced, which indicates a high risk of developing arrhythmias in CHF. In animals with CHF, the level of mRNA for Sigma₁-R in biopsy specimens of left ventricular myocardial tissue was found to increase by 74% (p = 0.0001) compared to the level of mRNA in the hearts of sham-operated rats, that apparently has compensatory character at maintaining proteostasis, modulating the activity of various ion channels and normalizing bioenergetic processes in the myocardium. Conclusion. Thus, with CHF in the left ventricle of the rat heart, gene expression of receptor and regulatory proteins involved in myocardial remodeling increases, which can be one of the mechanisms of violation of myocardial contractility and the occurrence of malignant heart rhythm disorders that make it difficult for the disease.