Entendendo os efeitos da Hipertensão Renovascular nas células da glia

• Processo: 24/21699-7
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Data de Início da vigência: 01 de abril de 2025
• Data de Término da vigência: 31 de março de 2026
• Área de conhecimento: Ciências Biológicas - Fisiologia - Fisiologia de Órgãos e Sistemas
• Pesquisador responsável: Lisete Compagno Michelini
• Beneficiário: Sany Martins Pérego
• Supervisor: Vinicia Campana Biancardi
• Instituição Sede: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brasil
• Instituição Anfitriã: Auburn University, Estados Unidos
• Vinculado à bolsa: 22/14337-6 - Efeitos da hipertensão renovascular e do treinamento físico na permeabilidade e alterações ultraestruturais da barreira hematoencefálica., BP.DR
• Assunto(s): Astrócitos Barreira hematoencefálica Hipertensão renovascular Microglia Fisiologia cardiovascular
• Palavra(s)-Chave do Pesquisador: astrócitos | Barreira hematoencefálica | hipertensão renovascular | microglia | Fisiologia Cardiovascular

Resumo

Elevated levels of Angiotensin II (AngII) contribute to blood-brain barrier (BBB) dysfunction in essential hypertension through mechanisms involving maladaptation of BBB membrane components, inflammation, and involvement of the innate immune system, among others. AngII-induced BBB dysfunction initiates a deleterious cycle that sustains the chronic phase of hypertension by allowing plasma AngII to access the brain parenchyma, particularly in cardiovascular nuclei that are normally protected by a functional barrier, thereby increasing sympathetic activity - a major characteristic or neurogenic hypertension. Previous work has primarily studied the mechanisms involved in BBB dysfunction in spontaneously hypertensive rats, where hypertension, although associated with AngII, involves multiple other pathways or in models using exogenously applied AngII, which do not accurately represent hypertension in a clinically relevant context. In this project, we will use the renovascular hypertensive model, a secondary form of hypertension driven mainly by AngII in its maintenance phase and commonly observed in clinical practice. Our previous studies have shown increased BBB disruption in this model, along with increased expression of aquaporin-4, a protein located in astrocyte end-feet that is selective for water transport in BBB. However, the role of inflammation, particularly involving astrocytes and microglia and its associated mechanism in renovascular hypertension has not yet been determined. Therefore, based on our preliminary data, we will test the hypotheses that glial cells (microglia and astrocytes) become reactive in renovascular hypertension, adopting a pro-inflammatory phenotype that leads to an increase in pro-inflammatory cytokines, which, in turn, correlates with increased BBB permeability and heightened sympathetic activity in renovascular hypertension.