NLRP3 Activation and Its Relationship to Endothelial Dysfunction and Oxidative Stress: Implications for Preeclampsia and Pharmacological Interventions

Author(s)

Nunes, Priscila Rezeck ; Mattioli, Sarah Viana ; Sandrim, Valeria Cristina

• Document type: Journal article
• Source: CELLS; v. 10, n. 11, p. 14-pg., 2021-11-01.

Abstract

Preeclampsia (PE) is a specific syndrome of human pregnancy, being one of the main causes of maternal death. Persistent inflammation in the endothelium stimulates the secretion of several inflammatory mediators, activating different signaling patterns. One of these mechanisms is related to NLRP3 activation, initiated by high levels of danger signals such as cholesterol, urate, and glucose, producing IL-1, IL-18, and cell death by pyroptosis. Furthermore, reactive oxygen species (ROS), act as an intermediate to activate NLRP3, contributing to subsequent inflammatory cascades and cell damage. Moreover, increased production of ROS may elevate nitric oxide (NO) catabolism and consequently decrease NO bioavailability. NO has many roles in immune responses, including the regulation of signaling cascades. At the site of inflammation, vascular endothelium is crucial in the regulation of systemic inflammation with important implications for homeostasis. In this review, we present the important role of NLRP3 activation in exacerbating oxidative stress and endothelial dysfunction. Considering that the causes related to these processes and inflammation in PE remain a challenge for clinical practice, the use of drugs related to inhibition of the NLRP3 may be a good option for future solutions for this disease. (AU)

• FAPESP's process: 20/14610-9 - Evaluation of pharmacological and molecular inhibition of NLRP3 inflammasome and its consequences in an in vitro model of Preeclampsia
• Grantee: Priscila Rezeck Nunes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/07230-8 - Arginase in preeclampsia: study of genetic polymorphism, circulating factors and in vitro assays
• Grantee: Valeria Cristina Sandrim
• Support Opportunities: Regular Research Grants