The Open Biochemistry Journal

ISSN: 1874-091X ― Volume 13, 2019

Heparin Alters Viral Serpin, Serp-1, Anti-Thrombolytic Activity to Anti-Thrombotic Activity

Xing Li1, Heather Schneider1, Andrew Peters1, Colin Macaulay1, Elaine King1, Yunming Sun1, 2, Liying Liu2, 3, Erbin Dai2, 3, Jennifer A Davids3, Grant McFadden2, 3, Alexandra Lucas*, 2, 3
1 Viron Therapeutics Inc., London, Ontario, Canada
2 Robarts Research Institute, Division of Cardiology Department of Medicine and Department of Microbiology and Im-munology, University of Western Ontario, London, Ontario, Canada
3 Department of Cardiovascular Medicine and Department of Molecular Genetics and Microbiology, University of Flor-ida, Gainesville, Florida, USA


Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and enhances Serp-1 inhibition of thrombin, a human pro-thrombotic serine protease, in vitro, altering inhibitory activity to a more predominant anti-thrombotic activity. Heparin also facilitates the simultaneous thrombin-mediated cleavage of Serp-1 and prevents formation of a serpin-typical SDS-resistant complex, implying mutual neutralization of Serp-1 and thrombin. In a cell-based assay, heparin facilitates Serp-1 reversal of cellular activation by stabilizing cellular membrane fluidity in thrombin-activated monocytes. In conclusion, heparin and other GAGs serve as cofactors enhancing Serp-1 regulation of local thrombotic and inflammatory pathways

Keywords: Serpin, heparin, myxoma virus, thrombosis, GAGs, thrombin.

Article Information

Identifiers and Pagination:

Year: 2008
Volume: 2
First Page: 6
Last Page: 15
Publisher Id: TOBIOCJ-2-6
DOI: 10.2174/1874091X00802010006

Article History:

Received Date: 28/11/2007
Revision Received Date: 8/1/2008
Acceptance Date: 17/1/2008
Electronic publication date: 6/2/2008
Collection year: 2008

Article Metrics:

CrossRef Citations:

Total Statistics:

Full-Text HTML Views: 1657
Abstract HTML Views: 1190
PDF Downloads: 278
Total Views/Downloads: 3125

Unique Statistics:

Full-Text HTML Views: 615
Abstract HTML Views: 590
PDF Downloads: 174
Total Views/Downloads: 1379
Geographical View

2008 Bentham Science Publishers Ltd.

* Address correspondence to this author at the Ethel Smith Endowed Chair, Professor, Department of Cardiovascular Medicine, University of Florida, 1600 SW Archer Road, Box 100277, Gainesville, FL 32610-0277. USA; Tel: 1-352-392-0092, 1-352-392-7424; Fax: 1-352-392-6662, E-mail:


"We have always had a fruitful cooperation and long-term experience of publishing with Bentham Open."

"A number of our original papers have appeared in its different journals, as the Bentham Open Publishers provides sufficient research in the field of science and technologies (belonging to the pharmaceutical, biotechnology, biomedical industries etc). The staff of the Bentham Open always treat our papers very seriously and gently during the rutile paper reviewing process, so far we always felt their kindness and highly cooperative support. Today, Bentham Open is providing a great support to science and research, giving opportunities of high standard publishing as well as promoting and enhancing selected papers around the world through communication and exchange of global scientific education."

Kholmirzo T. Kholmurodov
Leading Scientist
FLNP (Frank Laboratory of Neutron Physics) JINR (Joint Institute of Nuclear Research) Moscow region, Russia

Browse Contents

Webmaster Contact:
Copyright © 2019 Bentham Open