Potential pharmacological use of nebivolol in reversing the anti-angiogenic status of Pre-eclampsia

• Grant number: 24/10080-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2024
• End date: September 30, 2027
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Thainá Omia Bueno Pereira
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is defined by the American College of Obstetricians and Gynecologists as a pregnancy syndrome associated with hypertension, typically diagnosed after 20 weeks of gestation and often near term. The pathophysiology of the disease can be presented in two stages. The first stage involves the failure in the remodeling of maternal uterine spiral arteries, resulting in placental ischemia. The second stage is characterized by the release of anti-angiogenic factors into the maternal bloodstream, causing target organ damage. In this context, the imbalance between pro- and anti-angiogenic molecules impacts angiogenesis and vascular function, directly influencing key agents such as nitric oxide (NO), an important angiogenic mediator in endothelial cells. Although there are studies on the disease, including the discovery of new biomarkers and potential treatments, the most common pharmacological intervention in clinical practice remains the use of antihypertensive drugs. Nebivolol is a ²1-adrenergic receptor antagonist with vasodilatory properties mediated by agonistic action on the ²3-adrenergic receptor. This agonistic action increases NO levels through the activation of the ²3-adrenergic receptor and the enzyme endothelial nitric oxide synthase (eNOS) in endothelial cells incubated with plasma from pregnant women with PE. In this sense, the present study aims, in an unprecedented way, to evaluate angiogenic parameters of endothelial cells incubated with plasma from pregnant women with PE, in the presence or absence of nebivolol. Additionally, the possible dependence on the NO pathway in the angiogenic actions of nebivolol will be investigated. Exploring the impacts of the plasma and the drug on endothelial cells will enhance the understanding of the disease, contributing to the discovery of new biomarkers and pharmacological targets.