Patients with cirrhosis may display impaired or enhanced platelet activation, but the reasons for these equivocal findings are unclear. We investigated if bacterial lipopolysaccharide (LPS) is implicated in platelet activation. In a cross-sectional study, conducted in an ambulatory care clinic and hospital, comparing 69 cirrhosis patients and 30 controls matched for sex, age, and atherosclerotic risk factors, serum levels of LPS, soluble cluster of differentiation 40 ligand and p-selectin (two markers of platelet activation), and zonulin (a marker of gut permeability) were investigated. Ex vivo and in vitro studies were also performed to explore the effect of LPS on platelet activation. Compared to controls, cirrhosis patients displayed higher serum levels of LPS (6.0 [4.0-17.5] versus 57.4 [43.4-87.2] pg/mL, P < 0.0001), soluble cluster of differentiation 40 ligand (7.0 ± 2.2 versus 24.4 ± 13.3 ng/mL, P < 0.0001), soluble p-selectin (14.2 ± 4.05 versus 33.2 ± 15.2 ng/mL, P < 0.0001), and zonulin (1.87 ± 0.84 versus 2.54 ± 0.94 ng/mL, P < 0.006). LPS significantly correlated with zonulin (r = 0.45, P < 0.001). Ex vivo studies showed that platelets from cirrhosis patients were more responsive to the agonists independently from platelet count; this phenomenon was blunted by incubation with an inhibitor of Toll-like receptor 4. In vitro study by normal platelets showed that LPS alone (50-150 pg/mL) did not stimulate platelets but amplified platelet response to the agonists; Toll-like receptor 4 inhibitor blunted this effect. Conclusion: The study provides the first evidence that LPS may be responsible for platelet activation and potentially contributes to thrombotic complications occurring in cirrhosis.

Low-grade endotoxemia and platelet activation in cirrhosis / Raparelli, Valeria; Basili, Stefania; Carnevale, Roberto; Napoleone, Laura; DEL BEN, Maria; Nocella, Cristina; Bartimoccia, Simona; Lucidi, Cristina; Talerico, Giovanni; Riggio, Oliviero; Violi, Francesco. - In: HEPATOLOGY. - ISSN 0270-9139. - STAMPA. - 65:2(2017), pp. 571-581. [10.1002/hep.28853]

Low-grade endotoxemia and platelet activation in cirrhosis

RAPARELLI, Valeria;BASILI, Stefania;CARNEVALE, Roberto;NAPOLEONE, LAURA;DEL BEN, Maria;NOCELLA, CRISTINA;BARTIMOCCIA, SIMONA;Talerico, Giovanni;RIGGIO, Oliviero;VIOLI, Francesco
2017

Abstract

Patients with cirrhosis may display impaired or enhanced platelet activation, but the reasons for these equivocal findings are unclear. We investigated if bacterial lipopolysaccharide (LPS) is implicated in platelet activation. In a cross-sectional study, conducted in an ambulatory care clinic and hospital, comparing 69 cirrhosis patients and 30 controls matched for sex, age, and atherosclerotic risk factors, serum levels of LPS, soluble cluster of differentiation 40 ligand and p-selectin (two markers of platelet activation), and zonulin (a marker of gut permeability) were investigated. Ex vivo and in vitro studies were also performed to explore the effect of LPS on platelet activation. Compared to controls, cirrhosis patients displayed higher serum levels of LPS (6.0 [4.0-17.5] versus 57.4 [43.4-87.2] pg/mL, P < 0.0001), soluble cluster of differentiation 40 ligand (7.0 ± 2.2 versus 24.4 ± 13.3 ng/mL, P < 0.0001), soluble p-selectin (14.2 ± 4.05 versus 33.2 ± 15.2 ng/mL, P < 0.0001), and zonulin (1.87 ± 0.84 versus 2.54 ± 0.94 ng/mL, P < 0.006). LPS significantly correlated with zonulin (r = 0.45, P < 0.001). Ex vivo studies showed that platelets from cirrhosis patients were more responsive to the agonists independently from platelet count; this phenomenon was blunted by incubation with an inhibitor of Toll-like receptor 4. In vitro study by normal platelets showed that LPS alone (50-150 pg/mL) did not stimulate platelets but amplified platelet response to the agonists; Toll-like receptor 4 inhibitor blunted this effect. Conclusion: The study provides the first evidence that LPS may be responsible for platelet activation and potentially contributes to thrombotic complications occurring in cirrhosis.
2017
hepatology
01 Pubblicazione su rivista::01a Articolo in rivista
Low-grade endotoxemia and platelet activation in cirrhosis / Raparelli, Valeria; Basili, Stefania; Carnevale, Roberto; Napoleone, Laura; DEL BEN, Maria; Nocella, Cristina; Bartimoccia, Simona; Lucidi, Cristina; Talerico, Giovanni; Riggio, Oliviero; Violi, Francesco. - In: HEPATOLOGY. - ISSN 0270-9139. - STAMPA. - 65:2(2017), pp. 571-581. [10.1002/hep.28853]
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