title: Does NADPH oxidase deficiency cause artery dilatation in humans?
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 p47(phox) 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 p47(phox) 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 p47(phox) deficiency. Our observations lead to the hypothesis that oxidants are implicated in artery vasoconstriction.
authors.affiliation: Divisione I Clinica Medica, Department of Internal Medicine and Medical Specialities, University of Rome La Sapienza, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Loffredo
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Valerio
authors.initials: V
authors.lastname: Sanguigni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
authors.forename: Domenico
authors.initials: D
authors.lastname: De Mattia
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.forename: Baldassarre
authors.initials: B
authors.lastname: Martire
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pietrogrande
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gambineri
authors.forename: Giuliana
authors.initials: G
authors.lastname: Giardino
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Soresina
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000293:Adolescent; D001792:Blood Platelets / Q000201:enzymology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000503:physiopathology* / Q000652:urine; D006801:Humans; D028421:Isoprostanes / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency*; D014664:Vasodilation; D055815:Young Adult
chemical_list: D028421:Isoprostanes; D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1