title: Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study.
abstract: BACKGROUND
  NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD).
  
  
  RESULTS
  Twenty-five patients with hereditary deficiency of gp91(phox), the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91(phox), serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91(phox) expression was downregulated in X-CGD patients (1.0+/-0.8 mean fluorescence; P<0.001) and upregulated in obese patients (4.1+/-2.2 mean fluorescence; P=0.01) compared with healthy subjects (2.9+/-1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7+/-33.3 pg/mg creatinine; P=0.04) and increased in obese patients (154.4+/-91 pg/mg creatinine; P<0.001) compared with healthy subjects (69.5+/-52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3+/-6.7 versus 24.8+/-9.8 U/L; P<0.001) and X-CGD patients (28.5+/-7.2 U/L; P<0.001). X-CGD patients had significantly higher FMD (14.7+/-5.9%) compared with healthy subjects (7.9+/-2.5%; P<0.001); obese patients had lower FMD (5.3+/-3.0%; P=0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0+/-10.8 micromol/L; P=0.016) and lower in obese patients (9.3+/-11.0 micromol/L; P=0.001) compared with healthy subjects (27.1+/-19.1 micromol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R(s)=0.403, P<0.001) and platelet gp91(phox) (R(s)=-0.515, P<0.001). FMD inversely correlated with platelet gp91(phox) (R(s)=-0.502, P<0.001) and isoprostanes (R(s)=-0.513, P<0.001).
  
  
  CONCLUSIONS
  This study provides the first evidence that, in humans, gp91(phox) is implicated in the modulation of arterial tone.
authors.affiliation: Department of Experimental Medicine, Divisione I Clinica Medica, University of Rome La Sapienza, Rome, Italy. francesco.violi@uniroma1.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.forename: Valerio
authors.initials: V
authors.lastname: Sanguigni
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
authors.forename: Domenico
authors.initials: D
authors.lastname: De Mattia
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: Anna Rosa
authors.initials: AR
authors.lastname: Soresina
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
authors.forename: Stefania
authors.initials: S
authors.lastname: Basili
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Loffredo
mesh_terms: D000293:Adolescent; D000328:Adult; D001158:Arteries / Q000503:physiopathology*; D001792:Blood Platelets / Q000378:metabolism; D002648:Child; D015536:Down-Regulation; D006801:Humans; D028421:Isoprostanes / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000172:deficiency* / Q000652:urine; D008661:Metabolism, Inborn Errors / Q000503:physiopathology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000097:blood / Q000172:deficiency* / Q000652:urine; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009765:Obesity / Q000097:blood / Q000503:physiopathology / Q000652:urine; D012039:Regional Blood Flow; D015854:Up-Regulation; D014664:Vasodilation; D055815:Young Adult
chemical_list: D028421:Isoprostanes; D008562:Membrane Glycoproteins; D009566:Nitrates; D009573:Nitrites; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases