A non-anticoagulant synthetic pentasaccharide reduces inflammation in a murine model of kidney ischemia-reperfusion injury Academic Article uri icon

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abstract

  • SummaryFondaparinux is a synthetic pentasaccharide that selectively inhibits factor Xa (FXa) in an antithrombin-dependent fashion.This newly developed anticoagulant is used in the prevention and treatment of venous thromboembolism. Recently, we showed that fondaparinux reduces inflammation and protects the kidney from ischemia-reperfusion (I/R) injury. However, the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection is unknown.To address this, we chemically modified fondaparinux to abolish its affinity for antithrombin and analyzed the effect of this non-anti- coagulant (NAC)-pentasaccharide on binding of U937 cells to P-selectin in vitro and on inflammation in a murine model of kidney I/R injury. NAC-pentasaccharide was as effective as fondaparinux at inhibiting the binding of U937 cells to P-selectin.In addition, NAC-pentasaccharide significantly reduced IL-6 and MIP-2 expression and injury in the kidney I/R model.These findings indicate that the anti-inflammatory activity of fondaparinux can be dissociated from its anticoagulant activity and that NACpentasaccharide is protective in kidney I/R injury.

authors

  • Frank, Rolf
  • Holscher, Todd
  • Schabbauer, Gernot
  • Tencati, Michael
  • Pawlinski, Rafal
  • Weitz, Jeffrey
  • Mackman, Nigel

publication date

  • 2006

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