title: Phagocytic NADPH oxidase overactivity underlies oxidative stress in metabolic syndrome.
abstract: Oxidative stress plays a critical role in the pathogenesis of atherosclerosis in patients with metabolic syndrome. This study aimed to investigate whether a relationship exists between phagocytic NADPH oxidase activity and oxidative stress and atherosclerosis in metabolic syndrome patients. The study was performed in 56 metabolic syndrome patients (metabolic syndrome group), 99 patients with one or two cardiovascular risk factors (cardiovascular risk factor group), and 28 healthy subjects (control group). NADPH oxidase expression and activity was augmented (P < 0.05) in metabolic syndrome compared with cardiovascular risk factor and control groups. Insulin was enhanced (P < 0.05) in metabolic syndrome patients compared with cardiovascular risk factor and control groups and correlated with NADPH oxidase activity in the overall population. Insulin stimulated NADPH oxidase activity; this effect was abolished by a specific protein kinase C inhibitor. Oxidized LDL and nitrotyrosine levels and carotid intima-media thickness were increased (P < 0.05) in the metabolic syndrome group compared with cardiovascular risk factor and control groups and correlated with NADPH oxidase activity in the overall population. These findings suggest that phagocytic NADPH oxidase overactivity is involved in oxidative stress and atherosclerosis in metabolic syndrome patients. Our findings also suggest that hyperinsulinemia may contribute to oxidative stress in metabolic syndrome patients through activation of NADPH oxidase.
authors.affiliation: Area de Ciencias Cardiovasculares, Centro de Investigación Médica Aplicada, Avda. Pío XII 55, 31008 Pamplona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuño
authors.forename: Gorka
authors.initials: G
authors.lastname: San José
authors.forename: María U
authors.initials: MU
authors.lastname: Moreno
authors.forename: Oscar
authors.initials: O
authors.lastname: Beloqui
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Zalba
mesh_terms: D050197:Atherosclerosis; D015415:Biomarkers; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010586:Phagocytes / Q000201:enzymology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate