Low‐grade endotoxemia and platelet activation in cirrhosis
| Autor: | Valeria Raparelli, Stefania Basili, Laura Napoleone, Cristina Lucidi, Cristina Nocella, Giovanni Talerico, Oliviero Riggio, Roberto Carnevale, Maria Del Ben, Simona Bartimoccia, Francesco Violi |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Lipopolysaccharides Liver Cirrhosis Male medicine.medical_specialty Cirrhosis P-selectin 030204 cardiovascular system & hematology Severity of Illness Index Statistics Nonparametric NO bacterial lipopolysaccharide 03 medical and health sciences 0302 clinical medicine Reference Values Internal medicine Humans Medicine Platelet Platelet activation Receptor hepatology endotoxemia cirrhosis Platelet function Aged Intestinal permeability Hepatology Platelet Count business.industry Zonulin Middle Aged Platelet Activation medicine.disease Endotoxemia P-Selectin Cross-Sectional Studies Endocrinology Case-Control Studies Immunology Female 030211 gastroenterology & hepatology business Ex vivo |
| Zdroj: | Hepatology. 65:571-581 |
| ISSN: | 1527-3350 0270-9139 |
| Popis: | 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: LPS may be responsible for platelet activation and potentially contributes to thrombotic complications occurring in cirrhosis. (Hepatology 2017;65:571-581). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text