Endothelial dysfunction in preeclampsia: evaluation of potential new drugs in an in vitro model

• Grant number: 24/13523-6
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Agreement: CNPq
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Priscila Rezeck Nunes
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 24/01935-8 - Endothelial dysfunction in preeclampsia: evaluation of potential new drugs in an in vitro model, AP.R

Abstract

Preeclampsia (PE) is a syndrome specific to human pregnancy and is one of the main causes of maternal death worldwide. Half of patients with PE do not respond to current therapies and its pathophysiology is not yet fully understood. It is known that endothelial dysfunction, inflammation and oxidative stress are fundamentally important in this process. Persistent inflammation in the endothelium stimulates the secretion of several inflammatory mediators, which trigger an important process in inflammatory diseases by activating several signaling patterns. The present study aims to evaluate the effects of treatment with glibenclamide (GB) and metformin (MET) in cells incubated with plasma from pregnant women with PE and normotensive (NT) in relation to angiogenesis, inflammation, endothelial dysfunction and oxidative stress. The study also aims to perform a comprehensive analysis of circulating metabolites, focusing on amino acids and lipids, comparing the changes found in the plasma of pregnant women. To achieve this objective, the effect of drugs on the function of endothelial cells incubated with PE and NT plasma will be evaluated through angiogenesis assays, as well as the analysis of markers of endothelial dysfunction, oxidative stress assays and inflammatory markers. The metabolomic profile of plasma from pregnant women with PE and NT will also be analyzed using hydrogen nuclear magnetic resonance (NMR) spectroscopy. These investigations aim to contribute to a deeper understanding of the mechanisms of action and effects of drugs on different pathophysiological processes associated with PE in an in vitro model, in addition to providing insights into potential therapeutic approaches and underlying mechanisms of this important pregnancy syndrome. (AU)