Endogenous tissue factor pathway inhibitor in vascular smooth muscle cells inhibits arterial thrombosis.

Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor-mediated coagulation. TFPI is expressed by endothelial and smooth muscle cells in the vasculature. Endothelium-derived TFPI has been reported to play a regulatory role in arterial thrombosis. However, the role of endogenous TFPI in vascular smooth muscle cells (VSMCs) in thrombosis and vascular disease development has yet to be elucidated. In this TFPI mice crossbred with Sma-Cre mice were utilized to establish TFPI conditional knockout mice and to examine the effects of VSMC-directed TFPI deletion on development, hemostasis, and thrombosis. The mice with deleted TFPI in VSMCs (TFPI) reproduced viable offspring. Plasma TFPI concentration was reduced 7.2% in the TFPI mice compared with TFPI littermate controls. Plasma TFPI concentration was also detected in the TFPI (mice deleted TFPI in endothelial cells and cells of hematopoietic origin) mice. Plasma TFPI concentration of the TFPI mice was 80.4% lower (P < 0.001) than that of the TFPI mice. No difference in hemostatic measures (PT, APTT, and tail bleeding) was observed between TFPI and TFPI mice. However, TFPI mice had increased ferric chloride-induced arterial thrombosis compared with TFPI littermate controls. Taken together, these data indicated that endogenous TFPI from VSMCs inhibited ferric chloride-induced arterial thrombosis without causing hemostatic effects.