STUDY OF MICRORNAS IN THE GENESIS OF ENDOTHELIAL DAMAGE RESULTING FROM OXYGEN DEPRIVATION AND IMPACT OF TREATMENT WITH GLP-1 ANALOG (GLUCAGON-LIKE PEPTIDE 1) IN ASSOCIATION WITH SGLT2 INHIBITORS

Abstract

Obesity is characterized by excessive deposition of fat that can interfere with the normal metabolic process of the body. The accumulation of excessive macronutrients in adipose tissues promotes the secretion and release of inflammatory mediators, including interleukin-6 (IL-6), interleukin 1², tumor necrosis factor ± (TNF-±), leptin and stimulation of the monocyte chemoprotein protein. 1 (MCP-1), which subsequently reduce adiponectin production. This environment alters metabolic processes and generates a pro-inflammatory state influencing the endothelial dysfunction that is associated with the formation of atherosclerotic plaque. Recently, microRNAs have been described as the link between the endothelium and adipocyte function in obesity and insulin resistance. MicroRNAs are involved in post-transcriptional regulation of gene expression and can affect both the stability and translation of mRNA through their inhibition or destabilization of translation. The use of GLP-1 agonists and, more recently, renal tubular glucose transport inhibitors (SGLT2i), has been linked to greater preservation of renal function in obese patients with kidney disease. Although these effects can be partially credited to their indirect effects of glucose reduction and weight loss, recent evidence has indicated a potential direct protective effect on the vascular endothelium. Behavior, diet and exposure to toxins can affect the phenotype of subsequent generations through mechanisms of epigenetic transmission. Inferring that such adaptive cellular processes are fundamental to the pathophysiology of obesity-induced endothelial dysfunction, the aim of this study will be to evaluate the effect of treatment with liraglutide in association with sGLT2i on the regulation of microRNAs 21 and 126 and the involvement of HIF1a in the modulation of inflammation induced by oxygen deprivation in immortalized endothelial cells.