OBJECTIVES: This study sought to examine the expression and activity of the calcium-dependent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in human atherosclerotic coronary arteries. BACKGROUND: The NOX-based NADPH oxidases are major sources of reactive oxygen species (ROS) in human vessels. Several NOX homologues have been identified, but their relative contribution to vascular ROS production in coronary artery disease (CAD) is unclear; NOX5 is a unique homolog in that it is calcium dependent and thus could be activated by vasoconstrictor hormones. Its presence has not yet been studied in human vessels. METHODS: Coronary arteries from patients undergoing cardiac transplantation with CAD or without CAD were studied; NOX5 was quantified and visualized using Western blotting, immunofluorescence, and quantitative real-time polymerase chain reaction. Calcium-dependent NADPH oxidase activity, corresponding greatly to NOX5 activity, was measured by electron paramagnetic resonance. RESULTS: Both Western blotting and quantitative real-time polymerase chain reaction indicated a marked increase in NOX5 protein and messenger ribonucleic acid (mRNA) in CAD versus non-CAD vessels. Calcium-dependent NADPH-driven production of ROS in vascular membranes, reflecting NOX5 activity, was increased 7-fold in CAD and correlated significantly with NOX5 mRNA levels among subjects. Immunofluorescence showed that NOX5 was expressed in the endothelium in the early lesions and in vascular smooth muscle cells in the advanced coronary lesions. CONCLUSIONS: These studies identify NOX5 as a novel, calcium-dependent source of ROS in atherosclerosis.
OBJECTIVES: This study sought to examine the expression and activity of the calcium-dependent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in humanatherosclerotic coronary arteries. BACKGROUND: The NOX-based NADPH oxidases are major sources of reactive oxygen species (ROS) in human vessels. Several NOX homologues have been identified, but their relative contribution to vascular ROS production in coronary artery disease (CAD) is unclear; NOX5 is a unique homolog in that it is calcium dependent and thus could be activated by vasoconstrictor hormones. Its presence has not yet been studied in human vessels. METHODS: Coronary arteries from patients undergoing cardiac transplantation with CAD or without CAD were studied; NOX5 was quantified and visualized using Western blotting, immunofluorescence, and quantitative real-time polymerase chain reaction. Calcium-dependent NADPH oxidase activity, corresponding greatly to NOX5 activity, was measured by electron paramagnetic resonance. RESULTS: Both Western blotting and quantitative real-time polymerase chain reaction indicated a marked increase in NOX5 protein and messenger ribonucleic acid (mRNA) in CAD versus non-CAD vessels. Calcium-dependent NADPH-driven production of ROS in vascular membranes, reflecting NOX5 activity, was increased 7-fold in CAD and correlated significantly with NOX5 mRNA levels among subjects. Immunofluorescence showed that NOX5 was expressed in the endothelium in the early lesions and in vascular smooth muscle cells in the advanced coronary lesions. CONCLUSIONS: These studies identify NOX5 as a novel, calcium-dependent source of ROS in atherosclerosis.
Authors: Tomasz J Guzik; Jerzy Sadowski; Bartlomiej Guzik; Andrew Jopek; Boguslaw Kapelak; Piotr Przybylowski; Karol Wierzbicki; Ryszard Korbut; David G Harrison; Keith M Channon Journal: Arterioscler Thromb Vasc Biol Date: 2005-11-17 Impact factor: 8.311
Authors: Dan Sorescu; Daiana Weiss; Bernard Lassègue; Roza E Clempus; Katalin Szöcs; George P Sorescu; Liisa Valppu; Mark T Quinn; J David Lambeth; J David Vega; W Robert Taylor; Kathy K Griendling Journal: Circulation Date: 2002-03-26 Impact factor: 29.690
Authors: Davin Jagnandan; Jarrod E Church; Botond Banfi; Dennis J Stuehr; Mario B Marrero; David J R Fulton Journal: J Biol Chem Date: 2006-12-12 Impact factor: 5.157
Authors: Manish Mittal; Mohammad Rizwan Siddiqui; Khiem Tran; Sekhar P Reddy; Asrar B Malik Journal: Antioxid Redox Signal Date: 2013-10-22 Impact factor: 8.401
Authors: Augusto C Montezano; Dylan Burger; Tamara M Paravicini; Andreia Z Chignalia; Hiba Yusuf; Mahmoud Almasri; Ying He; Glaucia E Callera; Gang He; Karl-Heinz Krause; David Lambeth; Mark T Quinn; Rhian M Touyz Journal: Circ Res Date: 2010-03-25 Impact factor: 17.367
Authors: Pamela W M Kleikers; K Wingler; J J R Hermans; I Diebold; S Altenhöfer; K A Radermacher; B Janssen; A Görlach; H H H W Schmidt Journal: J Mol Med (Berl) Date: 2012-10-23 Impact factor: 4.599