Daniele Pastori1, Antonella Esposito2, Roberto Carnevale3, Simona Bartimoccia1, Marta Novo1, Alessandra Fantauzzi2, Francesco Di Campli2, Pasquale Pignatelli4, Francesco Violi1, Ivano Mezzaroma2. 1. Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy. 2. Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy. 3. 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. 4. Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy. Electronic address: pasquale.pignatelli@uniroma1.it.
Abstract
OBJECTIVES: 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.
OBJECTIVES:HIV-1patients 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-1patients 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: Morris Madzime; Theresa M Rossouw; Annette J Theron; Ronald Anderson; Helen C Steel Journal: Front Immunol Date: 2021-03-12 Impact factor: 7.561
Authors: Fabrice Cognasse; Anne Claire Duchez; Estelle Audoux; Theo Ebermeyer; Charles Antoine Arthaud; Amelie Prier; Marie Ange Eyraud; Patrick Mismetti; Olivier Garraud; Laurent Bertoletti; Hind Hamzeh-Cognasse Journal: Front Immunol Date: 2022-02-03 Impact factor: 7.561