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The NLRP3 role in erectile dysfunction in hypertensive model DOCA / salt and its possible activation by ET-1

Grant number: 16/07641-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2016
Effective date (End): January 31, 2020
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Fernando Silva Carneiro
Grantee:Rafael Sobrano Fais
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):18/05638-7 - The role of Calcium-Activated potassium channels 2.3 (KCa 2.3) in the inhibition of endothelin-1 (ET-1)-induced NLRP3 activation and impairment of the erectile function in DOCA/Salt model of arterial hypertension, BE.EP.DR

Abstract

Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection of the penis for satisfactory sexual intercourse. ED is often associated with risk factors for developing cardiovascular diseases such as hypertension and / or metabolic diseases such as diabetes and dyslipidemia. Hypertension has become a growing public health problem, it is an important risk factor for the onset of cardiovascular, cerebrovascular and renal diseases. Furthermore, ED occurs twice as frequently in patients with hypertension compared to normotensive patients. Vascular damage occur in hypertension, in part due to increased inflammatory mediators. Similarly, several studies have shown that increased expression of inflammatory mediators is closely linked to the development of ED. Both, the ED and hypertension are strongly influenced by the increased expression of endothelin-1 (ET-1), due to its contractile and pro-inflammatory effects. The NLRP3 receptor is the most studied member of the family inflammasome a multiprotein complex of the innate immune system triggers activation of caspase-1 and maturation of pro-inflammatory cytokines such as interleukin-1 beta (IL-l²). The increase in receptor activity NLRP3 promotes vascular disorders, cardiac and renal hypertrophy, and increase in blood pressure. However, it is still unknown whether the NLRP3 contributes to the proinflammatory action of ET-1. Hypothesis: The NLRP3 mediates pro-inflammatory effects of ET-1 model of hypertension DOCA / salt, which contributes to the genesis of ED in mice.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DAS GRACAS CORSI-ZUELLI, FABIANA MARIA; BROGNARA, FERNANDA; DA SILVA QUIRINO, GUSTAVO FERNANDO; HIROKI, CARLOS HIROJI; FAIS, RAFAEL SOBRANO; DEL-BEN, CRISTINA MARTA; ULLOA, LUIS; SALGADO, HELIO CESAR; KANASHIRO, ALEXANDRE; LOUREIRO, CAMILA MARCELINO. Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Acetylcholine the Alpha-7 nicotinic Acetylcholine Receptor. FRONTIERS IN IMMUNOLOGY, v. 8, MAY 31 2017. Web of Science Citations: 8.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.