Heme oxygenase-1 inducer hemin prevents vascular thrombosis

Nicolas Desbuards; Gaël Y. Rochefort; Deborah Schlecht; Marie-Christine Machet; Jean-Michel Halimi; Véronique Eder; Jean-Marc Hyvelin; Daniel Antier

doi:10.1160/TH06-12-0717

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(03): 614-620
DOI: 10.1160/TH06-12-0717

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Heme oxygenase-1 inducer hemin prevents vascular thrombosis

Nicolas Desbuards

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

,

Gaël Y. Rochefort

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

,

Deborah Schlecht

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

,

Marie-Christine Machet

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

,

Jean-Michel Halimi

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

,

Véronique Eder

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

,

Jean-Marc Hyvelin

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

,

Daniel Antier

¹LABPART – EA 3852 – IFR135 – Université François Rabelais, Tours Cedex 1, France

› Author Affiliations

Abstract

Summary

Hemin is a heme oxygenase-1 (HO-1) inducer which provides endogenous carbon monoxide known for playing roles in cell proliferation,inflammation or aggregation process. The objective of the current study was to examine the effect of prophylactic treatment with hemin in a thrombosis vascular model. Three groups of Wistar rats, control (n=6), hemin (n=6) and hemin+HO-1 inhibitor (n=6), were used for this study. Hemintreated animals received hemin (50 mg/kg/d; I.P.) for seven days and HO-1 inhibitor group received hemin at the same dose and SnPP IX (60 mg/kg/d; I.P.). All animals were exposed to electric stimulation of the left carotid according to Kawasaki’s procedure to induce reproducible thrombus formation. The hemin treatment did not induce blood pressure disturbance. Effects of hemin on vascular thrombosis were quantified by histopathology and its influence on haemostasis was assessed by measuring prothrombin time (PT), activated partial thromboplastin time (APTT) and blood parameters at the end of treatment. The HO-1 mRNA and protein level variation were also checked out. Results showed that chronic treatment with hemin significantly (p<0.01) reduced the vascular occlusion degree when compared to control and hemin SnPP groups with 7.2 ± 4.6 vs. 71.1 ± 14.7 and 74.0 ± 8.8%, respectively. Moreover, we observed significant (p<0.05) perturbations of blood parameters in hemintreated and hemin-SnPP treated rats. Interestingly, hemin treatment did not significantly increase both PT and APTT. Finally, the HO-1 mRNA and protein levels were increased in hemintreated carotid artery. In conclusion, hemin by inducing HO-1 expression may be a preventive agent against clinical disorders associated to an increased risk of thrombosis events and may limit haemorrhagic risks.

Keywords

Hemin - vascular thrombosis - rat

Full Text

References

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