Investigation of the Metformin role in angiogenesis and endothelial dysfunction in an in vitro model of preeclampsia

• Grant number: 24/03439-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2024
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Luís Fernando Pereira Passeti
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Pre-eclampsia (PE) is a hypertensive syndrome that occurs during pregnancy and represents one of the main causes of maternal mortality in Brazil and worldwide. Although the pathophysiology of PE is not yet completely understood, it is known that failure of trophoblastic invasion plays a fundamental role, resulting in placental ischemia and subsequent hypoxia. These events are significant since the release of products resulting from poor perfusion into the maternal circulation such as sFlt-1 (soluble fms -like tyrosine kinase-1) and sEng (soluble Endoglin) can trigger systemic endothelial dysfunction. These processes further corroborate the condition of ischemia, which hinders the supply of placental oxygen. That said, Metformin (MET), a drug used to treat type 2 diabetes, has shown promise in the treatment of hypertensive diseases of pregnancy. Data from the literature suggest cardioprotective, anti-inflammatory and antioxidant effects of this drug. However, in the present study, the focus will be the analysis of the effects of MET on endothelial cells cultured with plasma from pregnant women with PE and its impact on angiogenesis, endothelial dysfunction, oxidative stress as well as the expression of sFlt-1 and sEng. These effects will be observed by flow cytometry, tube formation, wound healing, DAF, CM-H2DCFDA, FRAP, western blotting and JC-1 assay techniques. The results obtained, together with data from the literature, will be important in the search to develop new treatments and more effective therapies for this pregnancy pathology.