PS-B02-6: CHANGES OF THE EXTRACELLULAR MATRIX AND INTERCELLULAR COMMUNICATION IN THE RAT HEARTS WITH VOLUME-PRESSURE OVERLOAD AND MODULATION BY CARDIOPROTECTIVE DRUGS

Abstract

Objective: Pathogenesis of heart failure (HF) and hypertension with a focus on extracellular matrix (ECM) and communication in the heart is still a current scientific topic that calls for new findings. Design and method: We used as experimental model normotensive (HSD) and hypertensive (TGR) rats with aortocaval fistula (ACF) supplemented with an ACE inhibitor (ACEi)(15weeks, 6 mg/L) and an AT1 receptor blocker (ARB)(15weeks, 200 mg/L). At the end of the experiments, serum and myocardial tissue samples of the right and left ventricles were taken for biometric, biochemical, gene, protein and microscopic analyzes. Results: We observed an increase in the cardiac weight index after ACF, left and right ventricles in HSD and TGR rats. ACEi and ARB have normalized this condition to a greater extent. Due to ACF, serum concentrations of ANP and TBARS were increased in the blood serum of both strains. ACF increased hydroxyproline levels in right ventricular levels in HSD and TGR rats and left ventricular TBARS in TGR rats. In addition, ACF increased mRNA collagenI, and collagenI protein expression in the left and right ventricles of HSD rats. In contrast, ACF reduced Cx43 and pCx43 protein levels in the left and right ventricles of both strains, SMAD2 expression in the right ventricle in HSD and TGR rats. ACF also suppressed MMP-2 protein expression in both cardiac ventricles in HSD rats and PKCepsilon protein expression in both heart chambers of both strains. Hypertension caused a slight decrease in the protein expression of Cx43, pCx43 and PKCepsilon and an increase in the expression of PKCdelta in cardiac ventricles of both rat strain. Hypertension further increased and collagenI in TGR rats in the left and right ventricles of the heart. Microscopic analyzes showed that ACF induced cardiomyocyte hypertrophy as well as decreased activity of enzymes involved in ACF energy metabolism. An interesting finding was that the signaling pathways involved in cardiac remodeling were more normalized by the ARB, while proteins involved in intercellular communication by ACEi. Conclusions: Based on the results obtained from the experiment, it can be stated that the right ventricle is more significantly affected by ACF and the results of analyzes in TGR indicate adaptation, attenuated responses to the parameters we observed. Supported by: APVV-21-410, VEGA-2/0158/19.