Abstract:
: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 TFPIFlox 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 (TFPISma) reproduced viable offspring. Plasma TFPI concentration was reduced 7.2% in the TFPISma mice compared with TFPIFlox littermate controls. Plasma TFPI concentration was also detected in the TFPITie2 (mice deleted TFPI in endothelial cells and cells of hematopoietic origin) mice. Plasma TFPI concentration of the TFPITie2 mice was 80.4% lower (P < 0.001) than that of the TFPIFlox mice. No difference in hemostatic measures (PT, APTT, and tail bleeding) was observed between TFPISma and TFPIFlox mice. However, TFPISma mice had increased ferric chloride-induced arterial thrombosis compared with TFPIFlox littermate controls. Taken together, these data indicated that endogenous TFPI from VSMCs inhibited ferric chloride-induced arterial thrombosis without causing hemostatic effects.
journal_name
Front Medjournal_title
Frontiers of medicineauthors
Yang J,Jin K,Xiao J,Ma J,Ma Ddoi
10.1007/s11684-017-0522-ysubject
Has Abstractpub_date
2017-09-01 00:00:00pages
403-409issue
3eissn
2095-0217issn
2095-0225pii
10.1007/s11684-017-0522-yjournal_volume
11pub_type
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