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

• Grant number: 24/01935-8
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2024
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Agreement: CNPq
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Valeria Cristina Sandrim
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 21/12010-7 - Endothelial dysfunction in hypertensive disorders of pregnancy, AP.TEM
• Associated scholarship(s): 24/13523-6 - Endothelial dysfunction in preeclampsia: evaluation of potential new drugs in an in vitro model, BP.JD

Abstract

Preeclampsia (PE) is a specific syndrome of human pregnancy, being one of the main causes of maternal death worldwide. Half of patients with PE do not respond to current therapies, and despite this, 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) on cells incubated with plasma from pregnant women with PE and normotensive (NT) concerning angiogenesis, inflammation, endothelial dysfunction, and oxidative stress. The study also aims to carry out a comprehensive analysis of circulating metabolites, focusing on amino acids and lipids, comparing the changes found in pregnant women's plasma. To achieve this objective, the effect of drugs on the function of endothelial cells incubated with PE and NT plasma will be carried out through angiogenesis assays, markers of endothelial dysfunction, oxidative stress, and inflammation, as well as analysis of the metabolomic profile of plasma from pregnant women with PE and NT 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, both at the cellular level and in in vivo models, in addition to providing insights into potential therapeutic approaches and underlying mechanisms of this important syndrome of gestation. (AU)