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Advances in vascular thiol isomerase function

Flaumenhaft, Robert

doi: 10.1097/MOH.0000000000000362
HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier
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Purpose of review The present review will provide an overview of several recent advances in the field of vascular thiol isomerase function.

Recent findings The initial observation that protein disulfide isomerase (PDI) functions in thrombus formation occurred approximately a decade ago. At the time, there was little understanding regarding how PDI or other vascular thiol isomerases contribute to thrombosis. Although this problem is far from solved, the past few years have seen substantial progress in several areas that will be reviewed in this article. The relationship between PDI structure and its function has been investigated and applied to identify domains of PDI that are critical for thrombus formation. The mechanisms that direct thiol isomerase storage and release from platelets and endothelium have been studied. New techniques including kinetic-based trapping have identified substrates that vascular thiol isomerases modify during thrombus formation. Novel inhibitors of thiol isomerases have been developed that are useful both as tools to interrogate PDI function and as potential therapeutics. Human studies have been conducted to measure circulating PDI in disease states and evaluate the effect of oral administration of a PDI inhibitor on ex-vivo thrombin generation.

Summary Current findings indicate that thiol isomerase-mediated disulfide bond modification in receptors and plasma proteins is an important layer of control of thrombosis and vascular function more generally.

Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to Robert Flaumenhaft, Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. Tel: +1 617 735 4005; fax +1 617 735 4000; e-mail: rflaumen@bidmc.harvard.edu

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