EFFECT OF DAPAGLIFLOZIN TREATMENT ON THE EXPRESSION OF MIRCRORNAS 126 AND 21 IN SPONTANEOUSLY HYPERTENSIVE RATS SUBMITTED TO A HYPERCALORIC DIET

• Grant number: 22/09850-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2022
• Effective date (End): July 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcelo Costa Batista
• Grantee: Kewellen Eduardo Silva Santos
• 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

Visceral obesity, the source of Metabolic Syndrome (MetS) is conceived as a pathophysiological basis related to the epidemic incidence of cardiovascular and renal events. The excessive expansion of adipose tissue causes an increase in the production of inflammatory proteins and the suppression of the anti-inflammatory cytokines synthesis involved in the etiopathogenesis of MS. Currently, epigenetics has emphasized the interaction of environmental factors, such as the easy access to caloric foods in genetic modifications, implying a greater risk in the progression of cardiovascular disease. In this scenario, micro-RNAs (miRNA) play an important role as post-transcriptional silencers, inhibiting the translation of target messenger RNA and influencing multiple signalling pathways, such as the regulation of insulin secretion and inflammatory protein synthesis. In addition, miRNAs are considered promising markers not only for early diagnosis, but also for monitoring the progression of kidney disease, diabetes and cardiovascular diseases, becoming targets of great interest among the scientific community. The SGLT-2 (Co-transporter Sodium-Glucose 2) protein responsible for the reabsorption of approximately 90% of renal glucose located predominantly in the proximal tubule, has its expression increased in patients with Diabetes Mellitus, participating in the pathophysiology inserted in the greatest risk for the development of cardiovascular and renal diseases in diabetic and obese people. In this way, the intervention on the SGLT-2 co-transporter has been used to address diabetes and insulin resistance, with a mechanism of action that is not restricted to greater renal glucose excretion. Therefore, the object of this work is to study the effect of treatment with Dapaglifozin, the SGLT-2 inhibitor, on miRNAs 126 and 21 in genetically hypertensive rats (SHR) submitted to a high calorie diet.