Effects of beta3-Adrenergic Activation on Endothelial Function in Cells Exposed to Pre-Eclamptic Placental Factors

• Grant number: 25/26328-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Ana Júlia Antunes Keller Rufini
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 25/13875-2 - Endothelial dysfunction in preeclampsia: use of the explant model as an alternative for drug studies, AP.R

Abstract

Preeclampsia (PE) is a gestational hypertensive syndrome characterized by blood pressure ¿140/90 mmHg, frequently accompanied by proteinuria and target organ dysfunction.¹ It affects 2-8% of pregnancies globally and represents one of the main causes of maternal and perinatal morbidity and mortality.¹ Its pathophysiology is described in two stages: initially, there is a failure in the remodeling of the uterine spiral arteries, leading to placental hypoperfusion; then, there is a release of antiangiogenic factors into the maternal circulation, resulting in endothelial dysfunction and vascular compromise.² This imbalance compromises the bioavailability of nitric oxide (NO), a fundamental mediator of endothelial function.³ Although there have been advances in understanding the disease, treatment is still predominantly based on the use of antihypertensive drugs.¹ In this context, the activation of the ¿3-adrenergic receptor in endothelial cells emerges as a promising pathway, by inducing endothelial nitric oxide synthase (eNOS), a precursor enzyme of NO, and favoring the production of the vasodilator, contributing to vascular homeostasis.⁴ Thus, this project proposes to investigate the effects of ¿3-adrenergic receptor agonism on NO production, viability, and cytotoxicity in endothelial cells exposed to supernatants of placental explants from pregnant women with preeclampsia. The objective is to evaluate the therapeutic potential of ¿3-adrenergic receptor activation in the face of a dysfunctional endothelial microenvironment.