Mechanisms underlying FeCl3-induced arterial thrombosis.
BACKGROUND
The FeCl(3)-induced vascular injury model is widely used to study thrombogenesis in vivo, but the processes leading to vascular injury and thrombosis are poorly defined.


OBJECTIVE
The aim of our study was to better characterize the mechanisms of FeCl(3)-induced vascular injury and thrombus formation, in order to evaluate the pathophysiological relevance of this model.


METHODS
FeCl(3) was applied at different concentrations (from 7.5% to 20%) and for different time periods (up to 5 min) to mouse carotid or mesenteric arteries.


RESULTS
Under all the conditions tested, ultrastructural analysis revealed that FeCl(3) diffused through the vessel wall, resulting in endothelial cell denudation without exposure of the inner layers. Hence, only the basement membrane components were exposed to circulating blood cells and might have contributed to thrombus formation. Shortly after FeCl(3) application, numerous ferric ion-filled spherical bodies appeared on the endothelial cells. Interestingly, platelets could adhere to these spheres and form aggregates. Immunogold labeling revealed important amounts of tissue factor at their surface, suggesting that these spheres may play a role in thrombin generation. In vitro experiments indicated that FeCl(3) altered the ability of adhesive proteins, including collagen, fibrinogen and von Willebrand factor, to support platelet adhesion. Finally, real-time intravital microscopy showed no protection against thrombosis in GPVI-immunodepleted and β(1)(-/-) mice, suggesting that GPVI and β(1) integrins, known to be involved in initial platelet adhesion and activation, do not play a critical role in FeCl(3)-induced thrombus formation.


CONCLUSIONS
This model should be used cautiously, in particular to study the earliest stage of thrombus formation.
UMR-S949 Inserm-Université de Strasbourg, Strasbourg, France.
A
A
Eckly
B
B
Hechler
M
M
Freund
M
M
Zerr
J-P
JP
Cazenave
F
F
Lanza
P H
PH
Mangin
C
C
Gachet
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002339:Carotid Arteries / Q000473:pathology* / Q000648:ultrastructure; D002712:Chlorides / Q000633:toxicity*; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy*; D014652:Vascular Diseases / Q000188:drug therapy*
D000925:Anticoagulants; D002712:Chlorides; D005290:Ferric Compounds; D010975:Platelet Aggregation Inhibitors; C024555:ferric chloride