Nitrite: a potencial drug for the treatment of endothelial dysfunction in preeclampsia

• Grant number: 23/10669-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2024
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Gabriela Morelli Zampieri
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is a disease that occurs in 2 to 8% of all pregnancies, and is a major cause of maternal and fetal mortality and morbidity. It is a hypertensive disease of pregnancy and can be characterized by an exaggerated production of reactive oxygen species (ROS), generalized inflammatory response, increase of antiangiogenic factors and endothelial dysfunction. Nitric oxide (NO) is an important regulator of vascular homeostasis and several studies have already demonstrated a decrease in NO levels in patients with PE. NO is produced from l-arginine by NOS enzymes (nitric oxide synthases), but it can also be produced through the nitrate-nitrite-NO pathway. The use of nitrite in cardiovascular diseases is an interesting treatment strategy, because in addition to increasing the bioavailability of NO, it has vasodilator, antihypertensive, angiogenic and antioxidant actions. With that in mind, the present study aims to use 2D and 3D cell cultures of HUVECs incubated with plasma from patients with PE to evaluate the effects of nitrite and propose its use in the treatment of PE. In addition, a proteomic analysis of these cells will be performed and specific inhibitors will be used to clarify the action pathways of nitrite.