Nox1 in cardiovascular diseases: regulation and pathophysiology

Author(s)

Gimenez, Marcela ^{[1, 2]} ; Schickling, Brandon M. ^[2] ; Lopes, Lucia R. ^[1] ; Miller, Jr., Francis J. ^{[2, 3]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[2] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 - USA

^[3] Vet Affairs Med Ctr Iowa City, Iowa City, IA 52246 - USA

• Document type: Review article
• Source: Clinical Science; v. 130, n. 3, p. 151-165, FEB 1 2016.
• Web of Science Citations: 16

Abstract

Since its discovery in 1999, a number of studies have evaluated the role of Nox1 NADPH oxidase in the cardiovascular system. Nox1 is activated in vascular cells in response to several different agonists, with its activity regulated at the transcriptional level as well as by NADPH oxidase complex formation, protein stabilization and post-translational modification. Nox1 has been shown to decrease the bioavailability of nitric oxide, transactivate the epidermal growth factor receptor, induce pro-inflammatory signalling, and promote cell migration and proliferation. Enhanced expression and activity of Nox1 under pathologic conditions results in excessive production of reactive oxygen species and dysregulated cellular function. Indeed, studies using genetic models of Nox1 deficiency or overexpression have revealed roles for Nox1 in the pathogenesis of cardiovascular diseases ranging from atherosclerosis to hypertension, restenosis and ischaemia/reperfusion injury. These data suggest that Nox1 is a potential therapeutic target for vascular disease, and drug development efforts are ongoing to identify a specific bioavailable inhibitor of Nox1. (AU)

• FAPESP's process: 13/18300-0 - Role of protein disulfide isomerase in the redox regulation of ADAM17 activation and EGFR signaling in vascular disease
• Grantee: Marcela Gimenez
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 13/03520-5 - Role of protein disulfide isomerase in NADPH oxidase dependent ROS generation during hypertension development
• Grantee: Lucia Rossetti Lopes
• Support type: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 09/54764-6 - Regulation of redox homeostasis and integrated stress response by Protein Disulfide Isomerase (PDI): mechanisms and role in the pathophysiology and therapy of vascular diseases
• Grantee: Francisco Rafael Martins Laurindo
• Support type: Research Projects - Thematic Grants