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

• Grant number: 16/07641-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2016
• Effective date (End): January 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Fernando Silva Carneiro
• Grantee: Rafael Sobrano Fais
• Host 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)

SOBRANO FAIS, RAFAEL; MENEZES DA COSTA, RAFAEL; CARVALHO MENDES, ALLAN; MESTRINER, FABIOLA; COMERMA-STEFFENSEN, SIMON GABRIEL; TOSTES, RITA C.; SIMONSEN, ULF; SILVA CARNEIRO, FERNANDO. NLRP3 activation contributes to endothelin-1-induced erectile dysfunction. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v. 27, n. 1, p. 14-pg., 2022-12-14. (16/07641-0, 18/05638-7, 16/11988-5, 19/19749-8)

FAIS, RAFAEL S.; RODRIGUES, FERNANDA L.; PEREIRA, CAMILA A.; MENDES, ALLAN C.; MESTRINER, FABIOLA; TOSTES, RITA C.; CARNEIRO, FERNANDO S.. The inflammasome NLRP3 plays a dual role on mouse corpora cavernosa relaxation (vol 9, 16224, 2019). SCIENTIFIC REPORTS, v. 10, n. 1, p. 1-pg., 2020-01-21. (18/05638-7, 16/07641-0, 16/11988-5)

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. (12/05178-0, 16/12195-9, 13/20549-7, 11/20343-4, 16/07641-0, 16/11988-5, 15/10378-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FAIS, Rafael Sobrano. Endothelin-1 role in NLRP3 activation in smooth muscle tissue of corpora cavernosa. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.