| Texto completo | |
| Autor(es): |
Santos, Karoliny Nune
;
Bizzotto, Juliana Q.
;
Bueno-Pereira, Thaina O.
;
Romao-Veiga, Mariana
;
Ribeiro-Vasques, Vanessa R.
;
Oliveira, Larissa Ragozo Cardoso
;
Sandrim, Valeria C.
;
Nunes, Priscila R.
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION; v. 45, n. 4, p. 13-pg., 2025-07-19. |
| Resumo | |
Preeclampsia (PE) is characterized by systemic endothelial dysfunction and remains a significant clinical challenge. Activation of NLRP3 inflammasome, reactive oxygen species (ROS) production, and pyroptosis and autophagy are important mechanisms in this condition. To evaluate the NLRP3 inhibitors effects: glibenclamide (GB) and MCC950, on markers of inflammation, endothelial dysfunction, cell death, and oxidative stress in an in vitro model of PE. Plasma from pregnant women with PE and normotensive pregnant women (NT) was used to investigate its impact on NLRP3 inflammasome activation (NLRP3, TLR4, MyD88, and caspase-1) in endothelial cells (ECs), analyzed by Western Blotting; effects of pharmacological inhibition on the function of ECs was assessed by the evaluation of permeability (VE-cadherin) and markers of endothelial dysfunction by flow cytometry (Flt-1, VEGFR2, E-selectin, VCAM-1, and ICAM-1), as well as cytotoxicity measured by lactate dehydrogenase (LDH), oxidative stress (ROS, nitric oxide - NO and antioxidant capacity), autophagy, and pyroptosis (interleukin IL-1 beta and high-mobility group box one - HMGB1). Both GB and MCC950 reduced NLRP3 inflammasome activation and its related effects in ECs exposed to PE plasma, including lowered IL-1 beta, caspase-1, modulated adhesion molecules expression, as well as decreased ROS and cytotoxicity. GB increased NO and restored VE-cadherin expression, while MCC950 enhanced antioxidant capacity. GB also induced autophagy, unlike MCC950. The NLRP3 inhibitors showed the potential to mitigate endothelial dysfunction, oxidative stress, and inflammation, suggesting both compounds hold potential therapeutic value for PE through distinct mechanisms. (AU) | |
| Processo FAPESP: | 24/01935-8 - Disfunção endotelial em pré-eclâmpsia: avaliação de potenciais novos fármacos em modelo in vitro |
| Beneficiário: | Valeria Cristina Sandrim |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 20/14610-9 - Avaliação da inibição farmacológica e molecular do inflamassoma NLRP3 e suas consequências em modelo in vitro de Pré-Eclâmpsia |
| Beneficiário: | Priscila Rezeck Nunes |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |