title: High glucose potentiates and renin-angiotensin blockade downregulates LPS-induced tissue factor expression in human mononuclear cells.
abstract: BACKGROUND
  Intimate links connect tissue factor (TF), the principal initiator of the clotting cascade, to inflammation, a cross-talk amplified by locally generated Angiotensin (ANG) II, the effector arm of the Renin Angiotensin System (RAS). The RAS, in turn, plays a pathophysiological role in diabetes, a proinflammatory state to which elevated glucose, the disease hallmark, contributes by activating key signalling pathways and increasing the cellular content of RAS components.
  
  
  OBJECTIVE
  To evaluate the effect of high glucose concentrations on TF antigen (Ag) expression and procoagulant activity (PCA) in lipopolysaccharide(LPS)-primed human mononuclear cell(MNC)s and to test whether pharmacological RAS blockade modifies that pattern.
  
  
  METHODS
  LPS-activated MNCs exposed to increasing D-glucose (from 5.5 to 50mM) in absence or presence of aliskiren, a renin inhibitor, zofenopril, an ANG converting enzyme inhibitor, and olmesartan, an ANGII type I receptor blocker. PCA was assessed by one-stage clotting assay and TF antigen expression by ELISA.
  
  
  RESULTS
  Increasing ambient glucose (range 5.5-50mM) potentiated LPS-induced PCA and TF Ag expression. Aliskiren, zofenopril and olmesartan downregulated those responses but the efficacy of the former decreased by ascending drug concentration while both zofenopril and olmesartan showed an opposite behaviour. TF Ag expression modulation by RAS blockade was stronger in 50 than 5mM ambient glucose.
  
  
  CONCLUSIONS
  High glucose potentiates the procoagulant action of LPS in human MNCs and RAS blockers downregulate that response possibly as a reflection of the underlying involvement of the system in that mechanism.
authors: Dipartimento Cardio Toracico e Vascolare, Università di Pisa, Italy.
authors: Cristina
authors: C
authors: Balia
authors: Silvia
authors: S
authors: Petrini
authors: Cinzia
authors: C
authors: Cordazzo
authors: Silvana
authors: S
authors: Cianchetti
authors: Tommaso
authors: T
authors: Neri
authors: Alessandro
authors: A
authors: Celi
authors: Roberto
authors: R
authors: Pedrinelli
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D013925:Thromboplastin; D005947:Glucose