Contribution of extracellular vesicles to cardiac alterations in CRS 3

Abstract

Cardiorenal Syndrome (CRS) is defined as a pathological relationship involving the kidneys and the heart, whose damage or injury to one of these organs is capable of leading to damage to the other organ. SCR is divided into five subtypes, according to the organ that was first injured and the period of injury (acute or chronic). SCR3 is characterized by acute kidney injury as a cause of cardiac injury, and has been the subject of laboratory research over the past 10 years. In this context, the research laboratory demonstrated the participation of the immune system, through TLR2 and 4 receptors and the cytokine IL-1², of the sympathetic nervous system, and confirmed the contribution of ROS and mitochondrial dysfunction in the development of SCR3. Also within the pathophysiology of SCRs, Extracellular Vesicles (EVs) were identified as participating in the communication between kidneys and heart through nucleic acids and proteins. With regard to nucleic, microRNAs (miRNAs) were also listed as contributors to kidney and heart diseases, regulating several pathways resulting from the deterioration of these organs. Given the above, this study aims to assess the participation of EVs produced by ischemic kidney injury in cardiac changes. Thus, the unilateral renal ischemia and reperfusion model will be performed for 60 minutes, followed by 8 days of renal reperfusion. Then, the vesicles present in the sera of ischemic and non-ischemic animals will be isolated, characterized and used for the treatment of cardiac cells of the H9C2 lineage. Thus, the expression of inflammation and cardiac trophism markers will be evaluated, in addition to the miRNAs identified as contributors to cardiac injury: miRNA-21, miRNA-24, miRNA-208 and miRNA-499. In a second moment, to evaluate the role of altered micro RNAs in this model, we will use the RNA interference technique, already implemented in our laboratory. (AU)