Assessment of the NLRP3 inflamassome's pharmacological inhibition regarding the gene expression of endothelial dysfunction markers in preeclampsia.

• Grant number: 23/00933-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2023
• Effective date (End): December 31, 2023
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Geovanna Carla Amaro da Silva
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is a human gestational disorder, one of Brazil's leading causes of obstetric maternal death. Although its physiopathology hasn't been completely elucidated, PE is related to placental ischemia, once the release of substances resulting from inadequate perfusion in the maternal circulation can lead to systemic endothelial dysfunction. These substances can behave like inflammatory mediators and activate the innate immune system promoting the escalation of numerous signal patches, which act on inflammasomes, a protein complex that mediates a highly inflammatory state, as a member of the NLR family pyrin domain containing 3 (NLRP3), the best described so far. In the face of systemic consequences caused by the intense inflammatory processes due to the inflammasome activation and considering that the causes related to endothelial dysfunction, oxidative stress, and inflammation in PE haven't been properly elucidated yet, the use of medication and molecular approaches related to NLRP3 pharmacological inhibition may be a good strategy to treat this disorder in the future. Some drugs such as glibenclamide (GB), a drug from the sulfonylurea family commonly prescribed to treat type 2 diabetes mellitus has been getting known to effectively inhibit inflammatory cell migration to NLPR3, acting on the improvement of endothelial dysfunction. Therefore, the present project aims to assess the pharmacological inhibition of the NLRP3 inflamassome through drugs like glibenclamide, regarding the gene expression of endothelial dysfunction markers on human umbilical veins endothelial cells (HUVEC) from healthy normotensive pregnant women (NT) and preeclamptic pregnant women (PE). Genes related to the inflammatory response, vasoconstriction, angiogenesis, oxidative stress, and hemostasis will be analyzed in HUVECs from the two aforementioned groups.