TY - JOUR
T1 - Lipopolysaccharide induces platelet activation in HIV patients
T2 - the role of different viral load patterns
AU - Nocella, Cristina
AU - Mezzaroma, Ivano
AU - Cammisotto, Vittoria
AU - Castellani, Valentina
AU - Milito, Cinzia
AU - Rugova, Alban
AU - Frati, Giacomo
AU - Pignatelli, Pasquale
AU - Violi, Francesco
AU - Pastori, Daniele
AU - Carnevale, Roberto
N1 - © 2021 British HIV Association.
PY - 2021/7
Y1 - 2021/7
N2 - OBJECTIVES: This study aimed to assess whether gut-derived lipopolysaccharide (LPS) could affect platelet function in HIV-1 patients with residual viral load.METHODS: In 23 HIV-1 patients on effective antiretroviral treatment, 10 treatment-naïve HIV-1 subjects and 20 healthy subjects (HS), LPS, zonulin, markers of platelet activation and oxidative stress were evaluated. In vitro, platelets from HS were exposed to plasma from HIV-1-infected treated and untreated patients.RESULTS: Compared with HS, LPS was higher in treated and treatment-naïve subjects with HIV-1 (7.7 ± 2.9, 80.9 ± 13.7 and 75.3 ± 22.6 pg/mL, P < 0.001 vs. HS) as well as serum zonulin (1.3 ± 0.5, 6.1 ± 1.5 and 5.3 ± 1.7 ng/mL, P < 0.001 vs. HS). LPS and zonulin were correlated in HIV patients (Spearman correlation coefficient (rS) = 0.73, P < 0.0001). Levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thromboxane B2 (TxB2 ) were higher in HIV-1-treated and treatment-naïve subjects compared with HS as well as NADPH oxidase 2 (NOX2) activation and hydrogen peroxide (H2 O2 ) production. In vitro, sCD40L, sP-selectin and TxB2 production, NOX2 activation and p47phox phosphorylation were higher in platelets exposed to plasma from HIV-1 patients with different viral load compared with the exposure to plasma from HS. This effect was blunted in platelets pre-treated with TLR4 or TLR7 inhibitors.CONCLUSIONS: Low-grade endotoxaemia and persistent viraemia increase platelet function with a mechanism mediated by NOX2 in patients with HIV-1 infection.
AB - OBJECTIVES: This study aimed to assess whether gut-derived lipopolysaccharide (LPS) could affect platelet function in HIV-1 patients with residual viral load.METHODS: In 23 HIV-1 patients on effective antiretroviral treatment, 10 treatment-naïve HIV-1 subjects and 20 healthy subjects (HS), LPS, zonulin, markers of platelet activation and oxidative stress were evaluated. In vitro, platelets from HS were exposed to plasma from HIV-1-infected treated and untreated patients.RESULTS: Compared with HS, LPS was higher in treated and treatment-naïve subjects with HIV-1 (7.7 ± 2.9, 80.9 ± 13.7 and 75.3 ± 22.6 pg/mL, P < 0.001 vs. HS) as well as serum zonulin (1.3 ± 0.5, 6.1 ± 1.5 and 5.3 ± 1.7 ng/mL, P < 0.001 vs. HS). LPS and zonulin were correlated in HIV patients (Spearman correlation coefficient (rS) = 0.73, P < 0.0001). Levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thromboxane B2 (TxB2 ) were higher in HIV-1-treated and treatment-naïve subjects compared with HS as well as NADPH oxidase 2 (NOX2) activation and hydrogen peroxide (H2 O2 ) production. In vitro, sCD40L, sP-selectin and TxB2 production, NOX2 activation and p47phox phosphorylation were higher in platelets exposed to plasma from HIV-1 patients with different viral load compared with the exposure to plasma from HS. This effect was blunted in platelets pre-treated with TLR4 or TLR7 inhibitors.CONCLUSIONS: Low-grade endotoxaemia and persistent viraemia increase platelet function with a mechanism mediated by NOX2 in patients with HIV-1 infection.
U2 - 10.1111/hiv.13059
DO - 10.1111/hiv.13059
M3 - Article
C2 - 33426758
VL - 22
SP - 434
EP - 444
JO - HIV Medicine
JF - HIV Medicine
SN - 1464-2662
IS - 6
ER -