Objective-NADPH oxidase, one of the most important enzymes producing reactive oxidant species, is suggested to play a role in experimental atherosclerosis, but its role in human atherosclerosis is still unclear. We hypothesized that a reduced activity of NADPH oxidase might be linked to a reduced atherosclerotic burden. Methods and Results-Thirty-one women carriers of hereditary deficiency of NOX2, the catalytic subunit of NADPH oxidase, were matched for sex and age with 31 controls and 31 obese women. Flow-mediated dilation and intima-media thickness, 2 surrogate markers of atherosclerosis, serum activity of NOX2, urinary isoprostanes, serum levels of nitrite/nitrate, and platelet production of isoprostanes and nitrite/nitrate were determined. Compared with controls (5.7 +/- 3.0% and 0.60 +/- 0.11 mm), carriers of NOX2 deficiency had higher flow-mediated dilation (9.2 +/- 5.0%; P<0.001) and lower intima-media thickness (0.50 +/- 0.11 mm; P=0.002), whereas obese women had lower flow-mediated dilation (3.2 +/- 2.1%; P=0.007) and higher intima-media thickness (0.71 +/- 0.15 mm; P<0.001). Compared with controls, carriers of NOX2 deficiency had lower urinary isoprostanes (132.6 +/- 87.3 versus 82.3 +/- 46.0 pg/mg creatinine; P=0.007) and serum NOX2 activity (24.9 +/- 19.3 versus 12.8 +/- 11.9 pg/mL; P=0.004) and higher serum nitrite/nitrate (23.8 +/- 7.6 versus 30.5 +/- 6.3 mu mol/L; P<0.001), whereas obese women had higher urinary isoprostanes (132.6 +/- 87.3 versus 182.2 +/- 84.6 pg/mg creatinine; P=0.008) and serum NOX2 activity (24.9 +/- 19.3 versus 36.1 +/- 18.6 pg/mL; P=0.008) and lower serum nitrite/nitrate (23.8 +/- 7.6 versus 12.6 +/- 4.2 mu mol/L; P<0.001). Flow-mediated dilation correlated with intima-media thickness (r=-0.433; P<0.001), serum NOX2 activity (r=-325; P<0.001), and urinary isoprostanes (r=-0.314; P=0.002). Ex vivo study showed that, compared with controls, platelets from carriers of NOX2 deficiency had lower isoprostanes (P<0.001) and higher nitrite/nitrate (P<0.001), whereas platelets from obese women had higher isoprostanes (P<0.001) and lower nitrite/nitrate (P=0.013). Conclusion-The study shows reduced atherosclerotic burden in carriers of NOX2 deficiency, suggesting that oxidative stress generated by this enzymatic pathway is implicated in human atherosclerosis. (Arterioscler Thromb Vasc Biol. 2013;33:406-412.)

Reduced Atherosclerotic Burden in Subjects With Genetically Determined Low Oxidative Stress / Violi, Francesco; Pignatelli, Pasquale; C., Pignata; A., Plebani; Rossi, Plinio; V., Sanguigni; Carnevale, Roberto; A., Soresina; Armando, Finocchi; E., Cirillo; Catasca, Elisa; Angelico, Francesco; Loffredo, Lorenzo. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 33:2(2013), pp. 406-+. [10.1161/atvbaha.112.300438]

Reduced Atherosclerotic Burden in Subjects With Genetically Determined Low Oxidative Stress

VIOLI, Francesco;PIGNATELLI, Pasquale;ROSSI, Plinio;CARNEVALE, Roberto;CATASCA, ELISA;ANGELICO, Francesco;LOFFREDO, Lorenzo
2013

Abstract

Objective-NADPH oxidase, one of the most important enzymes producing reactive oxidant species, is suggested to play a role in experimental atherosclerosis, but its role in human atherosclerosis is still unclear. We hypothesized that a reduced activity of NADPH oxidase might be linked to a reduced atherosclerotic burden. Methods and Results-Thirty-one women carriers of hereditary deficiency of NOX2, the catalytic subunit of NADPH oxidase, were matched for sex and age with 31 controls and 31 obese women. Flow-mediated dilation and intima-media thickness, 2 surrogate markers of atherosclerosis, serum activity of NOX2, urinary isoprostanes, serum levels of nitrite/nitrate, and platelet production of isoprostanes and nitrite/nitrate were determined. Compared with controls (5.7 +/- 3.0% and 0.60 +/- 0.11 mm), carriers of NOX2 deficiency had higher flow-mediated dilation (9.2 +/- 5.0%; P<0.001) and lower intima-media thickness (0.50 +/- 0.11 mm; P=0.002), whereas obese women had lower flow-mediated dilation (3.2 +/- 2.1%; P=0.007) and higher intima-media thickness (0.71 +/- 0.15 mm; P<0.001). Compared with controls, carriers of NOX2 deficiency had lower urinary isoprostanes (132.6 +/- 87.3 versus 82.3 +/- 46.0 pg/mg creatinine; P=0.007) and serum NOX2 activity (24.9 +/- 19.3 versus 12.8 +/- 11.9 pg/mL; P=0.004) and higher serum nitrite/nitrate (23.8 +/- 7.6 versus 30.5 +/- 6.3 mu mol/L; P<0.001), whereas obese women had higher urinary isoprostanes (132.6 +/- 87.3 versus 182.2 +/- 84.6 pg/mg creatinine; P=0.008) and serum NOX2 activity (24.9 +/- 19.3 versus 36.1 +/- 18.6 pg/mL; P=0.008) and lower serum nitrite/nitrate (23.8 +/- 7.6 versus 12.6 +/- 4.2 mu mol/L; P<0.001). Flow-mediated dilation correlated with intima-media thickness (r=-0.433; P<0.001), serum NOX2 activity (r=-325; P<0.001), and urinary isoprostanes (r=-0.314; P=0.002). Ex vivo study showed that, compared with controls, platelets from carriers of NOX2 deficiency had lower isoprostanes (P<0.001) and higher nitrite/nitrate (P<0.001), whereas platelets from obese women had higher isoprostanes (P<0.001) and lower nitrite/nitrate (P=0.013). Conclusion-The study shows reduced atherosclerotic burden in carriers of NOX2 deficiency, suggesting that oxidative stress generated by this enzymatic pathway is implicated in human atherosclerosis. (Arterioscler Thromb Vasc Biol. 2013;33:406-412.)
2013
atherosclerosis; nadph oxidase; oxidative stress
01 Pubblicazione su rivista::01a Articolo in rivista
Reduced Atherosclerotic Burden in Subjects With Genetically Determined Low Oxidative Stress / Violi, Francesco; Pignatelli, Pasquale; C., Pignata; A., Plebani; Rossi, Plinio; V., Sanguigni; Carnevale, Roberto; A., Soresina; Armando, Finocchi; E., Cirillo; Catasca, Elisa; Angelico, Francesco; Loffredo, Lorenzo. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 33:2(2013), pp. 406-+. [10.1161/atvbaha.112.300438]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/507509
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