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The synthetic pentasaccharide fondaparinux reduces coagulation, inflammation and neutrophil accumulation in kidney ischemia–reperfusion injury
Author(s) -
FRANK R. D.,
SCHABBAUER G.,
HOLSCHER T.,
SATO Y.,
TENCATI M.,
PAWLINSKI R.,
MACKMAN N.
Publication year - 2005
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2005.01188.x
Subject(s) - fondaparinux , acute kidney injury , inflammation , medicine , tissue factor , kidney , pharmacology , coagulation , renal ischemia , immunology , reperfusion injury , ischemia , thrombosis , venous thromboembolism
Summary. Ischemia–reperfusion (I/R) injury is associated with activation of coagulation and inflammation. Interestingly, various anticoagulants have been shown to reduce both coagulation and inflammation in animal models of kidney I/R injury. Fondaparinux is a synthetic pentasaccharide that selectively inhibits factor Xa (FXa) in the coagulation cascade. The aim of this study was to investigate the effect of fondaparinux in a lethal murine model of kidney I/R injury. A murine model of kidney I/R was established. In this model, we measured activation of the coagulation cascade and induction of inflammation. Administration of fondaparinux to I/R‐injured mice reduced fibrin deposition in the kidney, reduced serum creatinine levels and increased survival from 0 to 44% compared with saline‐treated control mice. Fondaparinux also reduced interleukin‐6 and macrophage inflammatory protein‐2 expression and decreased neutrophil accumulation in the injured kidneys. Finally, we showed that fondaparinux reduced thioglycollate‐induced recruitment of neutrophils into the peritoneum and inhibited the binding of U937 cells to P‐selectin in vitro . Our data suggest that fondaparinux reduces kidney I/R injury primarily by inhibiting the recruitment of neutrophils.