Factor XI contributes to thrombus propagation on injured neointima of the rabbit iliac artery.
BACKGROUND
Thrombus formation through the activation of tissue factor (TF) and factor (F) XI is a critical event in the onset of cardiovascular disease. TF expressed in atherosclerotic plaques and circulating blood is an important determinant of thrombogenicity that contributes to fibrin-rich thrombus formation after plaque disruption. However, the contribution of FXI to thrombus formation on disrupted plaques remains unclear.


METHODS
A mouse monoclonal antibody against FXI and activated FXI (FXIa) (XI-5108) was generated by immunization with activated human FXI. Prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time, and ex vivo platelet aggregation in rabbits were measured before and after an intravenous bolus injection of XI-5108. We investigated the role of FXI upon arterial thrombus growth in the rabbit iliac artery in the presence of repeated balloon injury.


RESULTS
The XI-5108 antibody reacted to the light chain of human and rabbit FXI/FXIa, and inhibited FXIa-initiated FXa and FXIa generation. Fibrin-rich thrombi developed on the injured neointima that was obviously immunopositive for glycoprotein IIb-IIIa, fibrin, TF, and FXI. Intravenous administration of XI-5108 (3.0 mg kg(-1)) remarkably reduced thrombus growth, and the APTT was significantly prolonged. However, PT, bleeding time and platelet aggregation were not affected.


CONCLUSIONS
These results indicate that plasma FXI plays a potent role in thrombus growth on the injured neointima. Inhibition of plasma FXI activity might help to reduce thrombus growth on ruptured plaques without prolonging bleeding time.
Yamashita
A
A
Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Nishihira
K
K
Kitazawa
T
T
Yoshihashi
K
K
Soeda
T
T
Esaki
K
K
Imamura
T
T
Hattori
K
K
Asada
Y
Y
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D001780:Blood Coagulation Tests; D005172:Factor XI / Q000502:physiology*; D015945:Factor XIa / Q000502:physiology*; D006801:Humans; D007083:Iliac Artery / Q000473:pathology*; D011817:Rabbits; D013927:Thrombosis / Q000209:etiology* / Q000517:prevention & control; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology*
D005172:Factor XI; D015945:Factor XIa