Identification and characterization of MicroRNAs regulated by metformin and related to endothelial dysfunction in an in vitro model of preeclampsia

• Grant number: 25/05516-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Daniela Alves Pereira
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is the main cause of worldwide maternal and perinatal morbimortality, however, over 40% of pregnant women do not respond to antihypertensive therapy, experience adverse events, and would benefit from a specific treatment. The pathophysiology of PE is not completely elucidated, but placental ischemia plays a fundamental role in the process, and the release of antiangiogenic factors is associated with the endothelial dysfunction present in PE. In this context, the expression of miRNAs changes throughout gestation and placental development, highlighting their importance in regulating the placentation. Metformin regulates the expression of several miRNAs, reduces endothelial dysfunction, and induces angiogenesis. Our hypothesis is that metformin regulates the expression of miRNAs that modulates the function of genes related to endothelial dysfunction in PE. Our objective is to identify miRNAs, their target genes, the biochemical pathways they participate in, related to endothelial dysfunction and regulated by metformin in an in vitro model of PE. The following experiments will be conducted: Identification and characterization of differentially expressed miRNAs using endothelial cells incubated with plasma from pregnant women with PE, normotensive women (NT), and metformin; and evaluation of the effect of miRNAs on migration, morphometry, and expression of molecules related to angiogenesis in endothelial cells incubated as per experiment described above. Results will be evaluated using parametric or non-parametric tests, with a significant value of p<0.05. We aim to identify miRNAs regulated by metformin and potential predictors of response; elucidate their role in relevant pathways for the pathophysiology of PE; and improve insight into the mechanisms involved in reducing endothelial dysfunction in PE. (AU)