Study of microRNAS in the genesis of endothelial injury resulting from oxygen deprivation and impact of treatment with GLP-1 analogue (GLUCAGON - LIKE PEPTIDE 1) in association with SGLT2 inhibitors

• Grant number: 24/19151-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2024
• End date: May 31, 2027
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcelo Costa Batista
• Grantee: Thais Silva de Jesus
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/25493-6 - Obesity: pathophysiology and related therapeutic strategies, AP.TEM

Abstract

Obesity is characterized by excessive fat deposition that can interfere with the processnormal metabolic rate 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 protein stimulationmonocyte chemoattractant. 1 (MCP-1), which subsequently reduce the production of adiponectin. This environment alters metabolic processes and generates a pro-inflammatory state influencing endothelial dysfunction that is associated with atherosclerotic plaque formation.Recently, microRNAs have been described as the link between the endothelium and the adipocyte function in obesity and insulin resistance. MicroRNAs are involved in post-transcriptional regulation of gene expression and can affect both stability andtranslation of mRNA through its inhibition or destabilization of translation. The use of GLP-1 agonists and, more recently, renal tubular glucose transport inhibitors (SGLT2i), has been related to greater preservation of renal function in obese patients with kidney disease. Although these effects can be partially credited to its indirect effects of glucose lowering and weight loss, recent evidence has indicated a potential protective effect directly into the vascular endothelium. Behavior, diet and exposure to toxins can affect phenotype of subsequent generations through epigenetic transmission mechanisms. Inferring that such Cellular adaptive processes are fundamental to the pathophysiology of endothelial dysfunction induced by obesity, the objective of this study will be to evaluate the effect of treatment with liraglutide in association with sGLT2i in the regulation of microRNAs 21 and 126 and the involvement ofHIF1a in modulating inflammation induced by oxygen deprivation in endothelial cells immortalized. (AU)