TY - JOUR
T1 - Does NADPH oxidase deficiency cause artery dilatation in humans?
AU - Loffredo, Lorenzo
AU - Carnevale, Roberto
AU - Sanguigni, Valerio
AU - Plebani, Alessandro
AU - Rossi, Paolo
AU - Pignata, Claudio
AU - De Mattia, Domenico
AU - Finocchi, Andrea
AU - Martire, Baldassarre
AU - Pietrogrande, Maria Cristina
AU - Martino, Silvana
AU - Gambineri, Eleonora
AU - Giardino, Giuliana
AU - Soresina, Anna Rosa
AU - Martino, Francesco
AU - Pignatelli, Pasquale
AU - Violi, Francesco
PY - 2013/4/20
Y1 - 2013/4/20
N2 - 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 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 p47phox deficiency. Our observations lead to the hypothesis that oxidants are implicated in artery vasoconstriction. Antioxid. Redox Signal. 18, 1491-1496.
AB - 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 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 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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U2 - 10.1089/ars.2012.4987
DO - 10.1089/ars.2012.4987
M3 - Article
C2 - 23216310
AN - SCOPUS:84875143983
VL - 18
SP - 1491
EP - 1496
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 12
ER -