title: Relationship between platelet and urinary 8-Iso-PGF2α levels in subjects with different degrees of NOX2 regulation.
abstract: BACKGROUND
  Urinary 8-iso-PGF2α, a marker of oxidative stress, is influenced by the activation of NOX2. It is unclear if platelets 8-iso-PGF2α contribute to urinary 8-iso-PGF2α.
  
  
  RESULTS
  In a cross-sectional study, platelet, urinary, and serum 8-iso-PGF2α were determined in subjects with downregulation (X-linked chronic granulomatous disease [X-CGD], n=25) and upregulation (type II diabetic patients [T2D], n=121) of NOX2 and 153 controls matched for sex and age. In diabetic patients (n=18), the above variables were repeated before and after 7 days treatment with 100 mg/day aspirin or 100 mg/day aspirin plus 40 mg/day atorvastatin. In vitro study was performed to see the contribution of blood cells to serum 8-iso-PGF2α. Compared with controls, X-CGD patients had lower platelet, serum, and urinary 8-iso-PGF2α values; conversely, diabetic patients had higher values of 8-iso-PGF2α compared with controls. Urinary 8-iso-PGF2α significantly correlated with both platelet and serum 8-iso-PGF2α in the 2 cohorts. A parallel increase of platelet, serum, and urinary 8-iso-PGF2α by aspirin and a parallel decrease by aspirin plus atorvastatin were detected in the interventional study. In vitro study demonstrated that platelets contribute to 37% of serum 8-iso-PGF2α and that only 13% of it is of extravascular origin.
  
  
  CONCLUSIONS
  The study suggests that NOX2 contributes to the formation of 8-iso-PGF2α in both platelets and urine. The direct correlation between platelet and urinary 8-iso-PGF2α suggests that, at least partly, urinary 8-iso-PGF2α reflects platelet 8-iso-PGF2α production. Analysis of serum 8-iso-PGF2α may represent a novel tool to investigate the production of 8-iso-PGF2α by blood cells including platelets.
  
  
  BACKGROUND
  URL: ClinicalTrials.gov. Unique Identifier: NCT01250340.
authors.affiliation: Clinica Medica, University of Rome "La Sapienza", Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Luigi
authors.initials: L
authors.lastname: Iuliano
authors.forename: Cristina
authors.initials: C
authors.lastname: Nocella
authors.forename: Simona
authors.initials: S
authors.lastname: Bartimoccia
authors.forename: Stefano
authors.initials: S
authors.lastname: Trapè
authors.forename: Roberta
authors.initials: R
authors.lastname: Russo
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gentile
authors.forename: Roberto
authors.initials: R
authors.lastname: Cangemi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Loffredo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000737:chemistry*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000652:urine; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: 8‐iso‐PGF2α; NOX2; oxidative stress; platelets