Nitrite as a Modulator of Inflammation and Endothelial Function in an in vitro model of Preeclampsia: Therapeutic Perspectives

• Grant number: 24/19683-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Valeria Cristina Sandrim
• 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 critical gestational condition that affects a large proportion of pregnancies worldwide and is responsible for thousands of maternal and fetal deaths annually. Hypertension and manifestations such as proteinuria and systemic inflammation are characteristic of the disease, resulting in persistent complications for mothers and babies. The pathophysiology of PE is related to a failure in placental vascular development, with inadequate remodeling of the spiral arteries, leading to ischemia and poor perfusion. As a consequence, factors that are harmful to the endothelium, such as reactive oxygen species (ROS), among others, are released, thus causing disruption in the release of substances such as nitric oxide (NO), essential for vascular regulation. In addition, damage to the endothelium can stimulate the production of pro-inflammatory cytokines and promote systemic inflammation, by activating pathways such as the NLRP3 inflammasome, an agent of the innate immune system. In addition to being a central agent in vasoregulation, NO has also been described as a possible inflammatory regulator, but there are reports of impairment of its synthesis by the classical pathway mediated by eNOS in PE. In this context, the use of nitrite as a NO donor appears as a promising alternative in the treatment of inflammation and its implications in PE. Despite this, there are still no studies exploring this potential in endothelial cells. Given this context, the objective of this project is to investigate the effects of nitrite, dependent or not on conversion to NO, on the NLRP3 pathway, in human umbilical vein endothelial cells (HUVECs) cultured with plasma from pregnant women with PE and its potential benefits.