Abstract

NADPH oxidase is known to modulate the arterial tone, but the role of its specific subunits is still unclear. The objective of this study was to compare the role of p47 and gp91phox (NOX2) on artery dilatation. We conducted a multicenter study enrolling 30 patients with chronic granulomatous disease (CGD) (25 with NOX2 deficiency and 5 with p47phox deficiency) and 30 healthy subjects (HS), matched for gender and age, in whom flow-mediated dilation (FMD), serum activity of NOX2 (soluble NOX2-derived peptide [sNOX2-dp]), urinary isoprostanes (8-iso-PGF2α), and platelet production of isoprostanes and NOX2 were determined. Compared to HS, patients with CGD had significantly higher FMD and lower sNOX2-dp and 8-iso-PGF2α levels. Compared to patients with NOX2 deficiency and HS, patients with p47phox hereditary deficiency had intermediate FMD and oxidative stress, that is, higher and lower FMD and lower and higher isoprostanes compared to HS and patients with NOX2 deficiency, respectively. In agreement with this finding, an ex vivo study showed higher inhibition of NOX2 activity and lower isoprostane formation in platelets from patients with NOX2 deficiency compared to platelets from ones with p47phox deficiency. Our observations lead to the hypothesis that oxidants are implicated in artery vasoconstriction. Antioxid. Redox Signal. 18, 1491–1496.

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References

1.
Cave ACBrewer ACNarayanapanicker ARay RGrieve DJWalker SShah AM. NADPH oxidases in cardiovascular health and diseaseAntioxid Redox Signal8691-7282006. 1. Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S, and Shah AM. NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 8: 691–728, 2006.
2.
Green DJJones HThijssen DCable NTAtkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter?Hypertension57363-92011. 2. Green DJ, Jones H, Thijssen D, Cable NT, and Atkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension 57: 363–9, 2011.
3.
Kuhns DBAlvord WGHeller TFeld JJPike KMMarciano BEUzel GDeRavin SSPriel DASoule BPZarember KAMalech HLHolland SMGallin JI. Residual NADPH oxidase and survival in chronic granulomatous diseaseN Engl J Med3632600-26102010. 3. Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, Uzel G, DeRavin SS, Priel DA, Soule BP, Zarember KA, Malech HL, Holland SM, and Gallin JI. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med 363: 2600–2610, 2010.
4.
Loffredo LMarcoccia APignatelli PAndreozzi PBorgia MCCangemi RChiarotti FVioli F. Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial diseaseEur Heart J28608-6122007. 4. Loffredo L, Marcoccia A, Pignatelli P, Andreozzi P, Borgia MC, Cangemi R, Chiarotti F, and Violi F. Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J 28: 608–612, 2007.
5.
Martire BRondelli RSoresina APignata CBroccoletti TFinocchi ARossi PGattorno MRabusin MAzzari CDellepiane RMPietrogrande MCTrizzino ADi Bartolomeo PMartino SCarpino LCossu FLocatelli FMaccario RPierani PPutti MCStabile ANotarangelo LDUgazio AGPlebani ADe Mattia D. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter studyClin Immunol126155-1642008. 5. Martire B, Rondelli R, Soresina A, Pignata C, Broccoletti T, Finocchi A, Rossi P, Gattorno M, Rabusin M, Azzari C, Dellepiane RM, Pietrogrande MC, Trizzino A, Di Bartolomeo P, Martino S, Carpino L, Cossu F, Locatelli F, Maccario R, Pierani P, Putti MC, Stabile A, Notarangelo LD, Ugazio AG, Plebani A, and De Mattia D. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study. Clin Immunol 126: 155–164, 2008.
6.
Pignatelli PCarnevale RCangemi RLoffredo LSanguigni VStefanutti CBasili SVioli F. Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemiaArterioscler Thromb Vasc Biol30360-3672010. 6. Pignatelli P, Carnevale R, Cangemi R, Loffredo L, Sanguigni V, Stefanutti C, Basili S, and Violi F. Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol 30: 360–367, 2010.
7.
van den Berg JMvan Koppen EAhlin ABelohradsky BHBernatowska ECorbeel LEspanol TFischer AKurenko-Deptuch MMouy RPetropoulou TRoesler JSeger RStasia MJValerius NHWeening RSWolach BRoos DKuijpers TW. Chronic granulomatous disease: the European experiencePLoS One4e52342009. 7. van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, Espanol T, Fischer A, Kurenko-Deptuch M, Mouy R, Petropoulou T, Roesler J, Seger R, Stasia MJ, Valerius NH, Weening RS, Wolach B, Roos D, and Kuijpers TW. Chronic granulomatous disease: the European experience. PLoS One 4: e5234, 2009.
8.
Violi FSanguigni VCarnevale RPlebani ARossi PFinocchi APignata CDe Mattia DMartire BPietrogrande MCMartino SGambineri ESoresina ARPignatelli PMartino FBasili SLoffredo L. Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter studyCirculation1201616-16222009. 8. Violi F, Sanguigni V, Carnevale R, Plebani A, Rossi P, Finocchi A, Pignata C, De Mattia D, Martire B, Pietrogrande MC, Martino S, Gambineri E, Soresina AR, Pignatelli P, Martino F, Basili S, and Loffredo L. Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study. Circulation 120: 1616–1622, 2009.
9.
Violi FSanguigni VLoffredo LCarnevale RBuchetti BFinocchi ATesauro MRossi PPignatelli P. Nox2 is determinant for ischemia-induced oxidative stress and arterial vasodilatation: a pilot study in patients with hereditary Nox2 deficiencyArterioscler Thromb Vasc Biol26e131-e1322006. 9. Violi F, Sanguigni V, Loffredo L, Carnevale R, Buchetti B, Finocchi A, Tesauro M, Rossi P, Pignatelli P. Nox2 is determinant for ischemia-induced oxidative stress and arterial vasodilatation: a pilot study in patients with hereditary Nox2 deficiency. Arterioscler Thromb Vasc Biol 26: e131–e132, 2006.

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Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 18Issue Number 12April 20, 2013
Pages: 1491 - 1496
PubMed: 23216310

History

Published in print: April 20, 2013
Published online: 14 March 2013
Published ahead of print: 7 December 2012
Accepted: 22 October 2012
Received: 17 October 2012

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Lorenzo Loffredo
Divisione I Clinica Medica, Department of Internal Medicine and Medical Specialities, University of Rome “La Sapienza,” Rome, Italy.
Roberto Carnevale
Divisione I Clinica Medica, Department of Internal Medicine and Medical Specialities, University of Rome “La Sapienza,” Rome, Italy.
Valerio Sanguigni
Department of Internal Medicine, University of Rome “Tor Vergata,” Rome, Italy.
Alessandro Plebani
Department of Pediatrics and Institute of Molecular Medicine “A. Nocivelli,” University of Brescia, Brescia, Italy.
Paolo Rossi
University-Hospital Pediatric Department, Bambino Gesù Children Hospital-University of Rome Tor Vergata, Rome, Italy.
Claudio Pignata
Department of Pediatrics, University of Naples, Naples, Italy.
Domenico De Mattia
Department of Biomedicine and Evolutive Aging, University of Bari, Bari, Italy.
Andrea Finocchi
University-Hospital Pediatric Department, Bambino Gesù Children Hospital-University of Rome Tor Vergata, Rome, Italy.
Baldassarre Martire
Department of Biomedicine and Evolutive Aging, University of Bari, Bari, Italy.
Maria Cristina Pietrogrande
IRCSS Foundation Ca’ Granda, University of Milan, Milan, Italy.
Silvana Martino
Department of Pediatrics, University of Turin, Turin, Italy.
Eleonora Gambineri
Department of Pediatrics, University of Florence, Florence, Italy.
Giuliana Giardino
Department of Pediatrics, University of Naples, Naples, Italy.
Anna Rosa Soresina
Department of Pediatrics and Institute of Molecular Medicine “A. Nocivelli,” University of Brescia, Brescia, Italy.
Francesco Martino
Department of Pediatrics, Center of Clinic Lipid Research, University of Rome “La Sapienza,” Rome, Italy.
Pasquale Pignatelli
Divisione I Clinica Medica, Department of Internal Medicine and Medical Specialities, University of Rome “La Sapienza,” Rome, Italy.
Francesco Violi
Divisione I Clinica Medica, Department of Internal Medicine and Medical Specialities, University of Rome “La Sapienza,” Rome, Italy.

Notes

Address correspondence to:Prof. Francesco VioliDivisione I Clinica MedicaDepartment of Internal Medicine and Medical SpecialitiesUniversity of Rome “La Sapienza”Viale del Policlinico 155Roma 00161Italy
E-mail: [email protected]

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