title: Vitamin E reduces monocyte tissue factor expression in cirrhotic patients.
abstract: Clotting activation may occur in liver cirrhosis, but the pathophysiological mechanism has not been fully elucidated. Because a previous study demonstrated that lipid peroxidation is increased in cirrhosis, we analyzed whether there is a relationship between lipid peroxidation and clotting activation. Thirty cirrhotic patients (19 men and 11 women; age, 34 to 79 years) and 30 controls matched for sex and age were investigated. In all subjects, monocyte expression of tissue factor (TF) antigen and activity; plasma levels of prothrombin fragment 1+2 (F1+2), a marker of thrombin generation; and urinary excretion of Isoprostane-F2alpha-III, a marker of lipid peroxidation, were measured. Furthermore, the above-reported variables were re-evaluated after 30 days of treatment with standard therapy (n = 5) or standard therapy plus 300 mg vitamin E twice daily (n = 9). In addition, we analyzed in vitro if vitamin E (50 micromol/L) influenced monocyte TF expression and F1+2 generation. Cirrhotic patients had higher values of Isoprostane-F2alpha-III (P <. 0001), F1+2 (P <.0001), and monocyte TF antigen (P <.0001) and activity (P <.03) than controls. Isoprostane-F2alpha-III was significantly correlated with F1+2 (Rho = 0.85; P <.0001) and TF antigen (Rho = 0.95; P <.0001) and activity (Rho = 0.94; P <.0001). After vitamin E treatment, Isoprostane-F2alpha-III (P =.008), F1+2 (P <.008), and monocyte TF antigen (P =.012) and activity (P =.008) significantly decreased; no changes of these variables were detected in patients not receiving vitamin E. In vitro, vitamin E significantly reduced the expression of monocyte TF antigen (-52%; P =.001) and activity (-55%; P =.003), as well as F1+2 generation (-51%; P =.025). This study shows that vitamin E reduces both lipid peroxidation and clotting activation and suggests that lipid peroxidation may be an important mediator of clotting activation in liver cirrhosis.
authors.affiliation: Department of Internal Medicine, I Clinica Medica, and Department of Therapeutic Medicine, University "La Sapienza," Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Ferro
authors.forename: S
authors.initials: S
authors.lastname: Basili
authors.forename: D
authors.initials: D
authors.lastname: Praticó
authors.forename: L
authors.initials: L
authors.lastname: Iuliano
authors.forename: G A
authors.initials: GA
authors.lastname: FitzGerald
authors.forename: F
authors.initials: F
authors.lastname: Violi
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000097:blood* / Q000628:therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D010919:Placebos; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012016:Reference Values; D013925:Thromboplastin / Q000096:biosynthesis*; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: C114340:8,12-iso-isoprostane F2alpha-III; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010919:Placebos; D011498:Protein Precursors; D014810:Vitamin E; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D013925:Thromboplastin; D015237:Dinoprost