Cardioprotective effect of angiotensin (1-7) in experimentally induced heart failure in rats
Authors: Sykora M , Kratky V , Tribulova N , Kopkan L , Szeiffova Bacova B 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 2/0158/19, VEGA 2/0002/20; Slovak Research and Development Agency APVV-15-0119, APVV-18-0548
The extracellular matrix (ECM) is a highly dynamic structure that affects the proper functioning of various tissues. ECM is involved in cell signaling, participates in the origin and development of pathology and its positive influence can result in improved disease. The pathophysiology of ECM also affects intercellular communication, which results in various arrhythmias in the heart. In the present work, we focused on the signaling pathways involved in cardiac structural remodeling due to volume overload, and at the same time, we tested the possibilities of the cardioprotective effect of angiotensin (1-7) (Ang (1-7)). As an experimental model of volume overload, we chose the aortocaval fistula (ACF) model, where we focused on the compensatory phase of heart failure. Male, 8 weeks old rats, from the normotensive Hannover Sprague-Dawley (HSD), the hypertensive Ren-2 of transgenic rats (TGR), and transgenic rats expressing the angiotensin (1-7) producing a fusion protein (TGR(A1-7)3292), we operationally created the ACF. 5 weeks after operation, the animals were decapitated and cardiac tissue samples were taken. Right and left ventricular tissue samples were used for biometric, biochemical, and proteomic analyzes. TGR(A1-7)3292 rats had significantly less hypertrophy compared to HSD and TGR after ACF. Hydroxyproline was increased in the TGR ACF group in both ventricles and in the right ventricle it was significantly reduced by Ang (1-7) compared to TGR ACF. In our selected proteins, the group of protein kinases C (PKC) α, δ, ε, matrix metalloproteinase 2 (MMP-2), SMAD2/3, connexin 43 (Cx43) and its phosphorylated form (pCx43) there were changes in protein levels, either due to hypertension after ACF, and in several cases the cardioprotective effect of Ang (1-7) was confirmed. PKCα and PKCδ showed a decrease in the TGR ACF group compared to HSD ACF and a decrease in the TGR(A1-7)3292 ACF group compared to HSD and TGR after ACF in both chambers. MMP-2 activity in the left and right ventricles had a reduced trend in the TGR and TGR(A1-7)3292 groups after ACF compared to HSD ACF. The same change occurred in MMP-2 protein expression in the right ventricle, in contrast to the left ventricle, where no change occurred. In the right ventricle, there was a decrease in SMAD2/3 protein expression in the TGR(A1-7)3292 group of ACF compared to HSD and TGR after ACF. Cx43 and pCx43 showed a very similar trend in both chambers, with an increase in the TGR ACF group versus HSD ACF, and the TGR(A1-7)3292 ACF versus HSD and TGR after ACF. Based on the obtained results, it can be stated that the right ventricle is more significantly affected by ACF and the endogenous production of Ang (1-7) alleviated the changes of the monitored proteins and the remodeling of the ECM caused by volume overload.