The role of Nox2 in endothelial dysfunction and failure of neutrophil migaration to focus of infection in sepsis

• Grant number: 12/24677-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 01, 2013
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Silvia Cellone Trevelin
• Supervisor: Ajay M. Shah
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: King's College London, England
• Associated to the scholarship: 11/03293-3 - Role of Nox2 derived products in the pathogenesis of sepsis, BP.DR

Abstract

Sepsis is a major cause of mortality in intensive care units. This syndrome develops when the host response to infection is inadequate resulting in bacteremia, systemic inflammation, cardiovascular collapse and death. Vascular dysfunction in sepsis may culminate in a state of shock characterized by prolonged hypotension, unresponsive to vasoconstrictor agents. This process results in multiple organ failure. The flavoprotein Nox2 is a major source of oxygen-derived reactive species (ROS) and its increased activity was related both to cardiovascular disease as infectious diseases. Since there are great synthesis and release of ROS during sepsis, we propose to investigate the role of endothelial Nox2 in vascular collapse and if it controls the migration of neutrophils to the site of the infection. We will induce sepsis in wild type and endothelial-specific down- expression of Nox2 trangenic mice and see: markers of organ damage (aspartate animotransferase, enzyme creatine kinase isoform MB and urea), blood pressure, synthesis of ROS in the heart and aorta, neutrophil sequestration in the lung, vascular function tests, quantification of bacteria in the blood and peritoneal lavage, and perform intravital microscopy in mesenteric bed. (AU)

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)

TREVELIN, SILVIA CELLONE; SAG, CAN MARTIN; ZHANG, MIN; ALVES-FILHO, JOSE CARLOS; CUNHA, THIAGO MATTAR; DOS SANTOS, CELIO XAVIER; SAWYER, GRETA; MURRAY, THOMAS; BREWER, ALISON; MARTINS LAURINDO, FRANCISCO RAFAEL; et al. Endothelial Nox2 Limits Systemic Inflammation and Hypotension in Endotoxemia by Controlling Expression of Toll-Like Receptor 4. Shock, v. 56, n. 2, p. 268-277, AUG 2021. (12/24677-7, 13/07937-8, 13/08216-2)

TREVELIN, SILVIA CELLONE; DOS SANTOS, CELIO XAVIER; FERREIRA, RAPHAEL GOMES; LIMA, LARISSA DE SA; SILVA, RANGEL LEAL; SCAVONE, CRISTOFORO; CURI, RUI; CARLOS ALVES-FILHO, JOSE; CUNHA, THIAGO MATTAR; ROXO-JUNIOR, PERSIO; et al. Apocynin and Nox2 regulate NF-kappa B by modifying thioredoxin-1 redox-state. SCIENTIFIC REPORTS, v. 6, OCT 4 2016. (12/24677-7, 09/54764-6, 13/08216-2, 13/03520-5, 11/19670-0, 11/03293-3, 13/07937-8)