Submitted May 18, 2007
Accepted September 19, 2008
Vascular smooth muscle-derived tissue factor is critical for arterial thrombosis after ferric chloride-induced injury
Li Wang, Christine Miller, Robert F Swarthout, Mohan Rao, Nigel Mackman, and Mark B Taubman*
Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester, Rochester, NY, United States
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
* Corresponding author; email: mark_taubman{at}urmc.rochester.edu.
Tissue factor (TF) initiates coagulation, regulates hemostasis and plays a critical role in mediating arterial thrombosis. TF is upregulated in vascular smooth muscle cells (VSMC) in atherosclerosis and arterial injury. To examine the biologic role of VSMC-derived TF we crossed TFflox/flox 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 TF VSMC-deficient mice. Stable occlusion was seen in 11/12 wild type mice, but in only 6/16 TF VSMC-deficient mice (p = 0.001). 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.
