Evaluation of the function of endothelial cells against the inhibition of NLRP3 inflammasome in an in vitro model of preeclampsia

• Grant number: 23/10917-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2024
• Effective date (End): December 31, 2024
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Priscila Rezeck Nunes
• Grantee: Karoliny Nunes dos Santos
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is a multisystem gestational disease characterized by arterial hypertension, proteinuria and placental ischemia. The set of symptoms and consequences of this pathology can generate several complications, such as impaired fetal neurological development, decreased mother's life expectancy and increased risk of developing various diseases, including cardiovascular disease, stroke and diabetes, making it one of the main causes of death maternal and fetal in Brazil and in the World. One of the possible causes of this pathology is the generalized dysfunction of the maternal endothelium, which alters several adaptive characteristics of the placenta, such as its controlled immune response to the fetus, changes in blood flow, among other adaptations typical of pregnancy. These changes are usually mediated by factors released by the placenta, which once deregulated cause the most varied dysfunctions, such as systemic inflammation. Despite several recent studies associating the main causes of PE with placental/endothelial dysfunction, studies are still needed to better understand the pathophysiology of the disease, helping in the search for prevention and treatment. This project aims to evaluate the pharmacological action of NLRP3 inflammasome inhibitors in an in vitro model of PE and the relationships with biomarkers of endothelial dysfunction and cell death. For this, assays will be carried out with human umbilical vein endothelial cells (HUVEC) incubated with plasma from pregnant women with PE and normotensive (NT) and the function of the endothelial cell will be analyzed through assays of tube formation, permeability, and cell death by autophagy and pyroptosis. The results will be evaluated by parametric or non-parametric tests, depending on their variability, adopting a significance level of p<0.05. Studies on endothelial dysfunction and its relationship with inflammation in PE still remain a goal to be further explored and may be favorable for developing new treatments and more effective therapies