title: HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity.
abstract: OBJECTIVE
  HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress.
  
  
  METHODS
  We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naïve HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F2α (8-iso-PGF2α).
  
  
  RESULTS
  sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p < 0.001). Platelet sNOX2-dp and 8-iso-PGF2α were significantly higher in HIV-1 naïve subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p < 0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p < 0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels.
  
  
  CONCLUSIONS
  HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress.
authors.affiliation: Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.affiliation: Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.affiliation: Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bartimoccia
authors.affiliation: Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Novo
authors.affiliation: Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fantauzzi
authors.affiliation: Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Campli
authors.affiliation: Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy. Electronic address: pasquale.pignatelli@uniroma1.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.affiliation: Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.affiliation: Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000821:virology*; D023201:CD40 Ligand / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D015539:Platelet Activation
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: HIV-1; Isoprostanes; NOX; Platelet activation