ACTIVE SITE INHIBITED FACTOR VIIA HAS A PROTECTIVE ROLE IN RENAL ISCHEMIA/REPERFUSION INJURY VIA ANTI-INFLAMMATORY MECHANISMS

Abstract number: P-M-010

Loubele¹ S.T.B.G., Leenders¹ P., van Oerle¹ R., Hamulyak² K., Buurman³ W.A., Spronk¹ H.M.H., van der Voort¹ D., ten Cate¹ H.

¹¹Department of Internal Medicine, Laboratory for Clinical Thrombosis and Haemostasis ²²Div. of Haematology, Cardiovascular Research Institute Maastricht, Maastricht University ³³Department of General Surgery, Nutrition and Toxicology Research Institute Maastricht, Maastricht, Netherlands

How-to-cite Loubele STBG, Leenders P, van Oerle R, Hamulyak K, Buurman WA, Spronk HMH, van der Voort D, ten Cate H. ACTIVE SITE INHIBITED FACTOR VIIA HAS A PROTECTIVE ROLE IN RENAL ISCHEMIA/REPERFUSION INJURY VIA ANTI-INFLAMMATORY MECHANISMS. J Thromb Haemost 2007; 5 Supplement 2: P-M-010

Abstract

Introduction: Renal ischemia/reperfusion (IR) has a great impact on graft survival after kidney transplantation. Inflammation and apoptosis are known to be of influence in renal IR injury but the exact mechanisms still need to be established. We investigated the effects of the anticoagulants active site inhibited factor VIIa (ASIS) and activated protein C (APC) on renal IR in mice.

Methods: Ischemia was induced in C57/Bl6J mice by placing a clamp on the left renal artery and vein. After 1 hr the clamp was released and the collateral kidney was removed. Reperfusion was induced for 2 hrs. Mouse ASIS (1 mg/kg), mouse APC (0.4 mg/kg) or placebo (0.9% NaCl) were administered iv 15 min before induction of reperfusion and 5 min after induction of reperfusion.

Results: Infarct sizes were not different between groups. IR increased TF activity in the left kidneys of placebo treated animals (41.98.9 pM) compared to sham animals (28.73.2 pM) (p< 0.05 for all indicated differences), whereas ASIS decreased TF activity levels in left (6.73.0 pM) and right (8.04.5 pM) kidneys compared to placebo. APC did not alter TF activity. IL-6 levels were below the detection limit in left kidneys of the sham group and in right kidneys of all groups. IR induced IL-6 in the left kidney of placebo treated animals (365.9 pg/ml) and ASIS reduced the IL-6 levels to undetectable levels, whereas APC did not decrease IL-6 (463.4 pg/ml) compared to placebo. PAI-1 antigen levels were increased in the left kidneys of placebo (1.30.3 ng/ml) compared to the sham group (1.10.03 ng/ml) and administration of ASIS or APC did not alter the PAI-1 levels. ASIS increased PAI-1 levels in the right kidneys (0.90.03 ng/ml) compared to placebo (0.40.6 ng/ml).

Conclusions: In a model of renal IR, inhibition of the FVIIa-TF complex attenuates inflammation, indicated by suppressed IL-6 levels. Furthermore, ASIS stimulates PAI-1 release during ischemia, which may indicate a link with angiogenesis. The net benefit for renal IR recovery needs further study.

To cite this abstract use the following format:

Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number

Session Details

Date:	01/08/2007
Time:	00:00-00:00
Session name:	XXIst ISTH Congress
Subject:
Location:	Oxford, UK
Presentation type:
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