Long-term modulation of lipoproteins metabolism induced by the use of glucocorticoids during pregnancy

• Grant number: 21/12441-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2022
• End date: October 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Silvana Auxiliadora Bordin da Silva
• Grantee: Carolina Vieira Campos
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Preterm birth is associated with higher risk of metabolic and cardiovascular disorders as well as Hypercholesterolemia and Atherosclerosis in mothers over the course of life. The role of miRNAs in this model is not yet characterized, but it is known that the miR-33 family controls ABCA1 and ABCG1 genes, involved in lipid metabolism, and exosome levels of miR-92 may interfere with brown adipose tissue function. Previous data from our laboratory showed that glucocorticoid treatment in preterm pregnant women may be a crucial factor in this process since it is related to higher adiposity and changes in maternal biochemical parameters, besides the modulation of miRNA levels carried by lipoproteins. Objectives: The central aim of this project is to evaluate long-term changes in the profile of miRNAs involved in lipid metabolism and associate them with the risk of developing metabolic disorders with potential coronary events in rats treated with glucocorticoids during pregnancy. Methods: Female Wistar rats treated or not with dexamethasone during the last third of pregnancy (days 14-19) will be used. At one year of age, the mother rats will be euthanized to collect blood, liver, and adipose tissue. The samples will be used for miRNA analysis by qPCR and protein expression of main targets by western blot. Culture of THP-1 cells will be performed to identify whether miR-92 and miR-33 modulate the expression of target genes ABCA1 and ABCG1 in women who received corticotherapy during pregnancy. (AU)