The effect of vascular smooth muscle cell-targeted expression of tissue factor pathway inhibitor in a murine model of arterial thrombosis

Thrombosis and Haemostasis
Shuchong PanRobert D Simari

Abstract

Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that regulates the extrinsic pathway of coagulation by inhibiting the factor VIIa/tissue factor (TF) catalytic complex. TFPI is expressed by both endothelial and smooth muscle cells in the vasculature and circulates at low levels. The role of local vascular TFPI in thrombosis and the development of vascular disease is unknown. To establish an experimental animal model to directly modulate smooth muscle cell-derived TFPI on the development of arterial thrombosis, transgenic mice in which a cDNA encoding murine TFPI is expressed from the murine SM22alpha promoter were generated. Expression of transgenic mRNA was 4-fold higher than the level of endogenous TFPI mRNA in arteries from transgenic mice. In situ hybridization confirmed that expression of the transgene was limited to medial vascular smooth muscle cells. Vascular TFPI activity was increased to 2 to 3-fold in carotid homogenates. There was no difference in plasma TFPI levels or hemostatic measures (PT, aPTT and tail vein bleeding times) between these mice and their wildtype littermates. In a ferric chloride-induced model of carotid thrombosis, homozygotic transgenic mice demonstrated resistance to t...Continue Reading

Citations

Aug 4, 2009·American Journal of Respiratory Cell and Molecular Biology·Thomas A WhiteRobert D Simari
Oct 23, 2010·European Heart Journal·Børge G NordestgaardUNKNOWN European Atherosclerosis Society Consensus Panel
Jan 1, 2010·Journal of Oral Microbiology·Amir E ZeituniChristopher W Cutler
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·George J Broze, Thomas J Girard
Aug 22, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Douglas A SimonettoVijay H Shah
Jul 19, 2017·BMC Cardiovascular Disorders·Ying ZhaoXiaoli Tian
Sep 10, 2009·Circulation·David R HolmesRobert D Simari
Jun 14, 2017·Journal of Cellular Physiology·Gianna FerrettiAmirhossein Sahebkar
Sep 12, 2012·Current Cardiology Reports·Ian GrahamZeljko Reiner
Mar 21, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Nigel Mackman, Mark B Taubman
Jan 10, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Eric W HolroydRobert D Simari
Feb 16, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Jianbo WuWilliam P Fay
Nov 25, 2020·Current Opinion in Endocrinology, Diabetes, and Obesity·Natalie C WardGerald F Watts

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