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Blood, 15 January 2009, Vol. 113, No. 3, pp. 705-713.
Prepublished online as a Blood First Edition Paper on October 17, 2008; DOI 10.1182/blood-2007-05-090944.
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THROMBOSIS AND HEMOSTASIS
Vascular smooth muscle–derived tissue factor is critical for arterial thrombosis after ferric chloride–induced injury
Li Wang1,
Christine Miller1,
Robert F. Swarthout1,
Mohan Rao1,
Nigel Mackman2, and
Mark B. Taubman1
1 Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester, NY; and
2 Department of Medicine, University of North Carolina at Chapel Hill
Tissue factor (TF) initiates coagulation, regulates hemostasis, and plays a critical role in mediating arterial thrombosis. TF is up-regulated in vascular smooth muscle cells (VSMCs) in atherosclerosis and arterial injury. To examine the biologic role of VSMC-derived TF, we crossed TFflox/flox mice with SM22 Cre+/– mice. TF mRNA and activity were decreased in the aortic media of TF-deficient mice by 96% and 94.8%, respectively. There were no differences in TF activity measured in plasma or concentrated microparticles. TF-deficient mice were generated with the expected frequency, showed no evidence of bleeding or increased mortality, and had similar activated partial thromboplastin and tail vein bleeding times. Thrombus-mediated flow reduction in response to ferric chloride injury of the carotid arteries was significantly attenuated in VSMC-specific TF-deficient. Stable occlusion was seen in 11 of 12 wild-type mice, but in only 6 of 16 VSMC-specific TF-deficient mice (P = .001). These data suggest that VSMC-derived TF is critical in a macrovascular model of arterial thrombosis. This mouse model should be valuable in determining the contribution of VSMC-derived TF in other TF-mediated phenomena, such as restenosis.

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