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Arterioscler Thromb Vasc Biol. 2015 Jan;35(1):16-23. doi: 10.1161/ATVBAHA.114.303410. Epub 2014 Aug 7.

Therapeutic implications of protein disulfide isomerase inhibition in thrombotic disease.

Author information

1
From the Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. rflaumen@bidmc.harvard.edu.
2
From the Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Erratum in

Abstract

The study of thrombus formation has increasingly applied in vivo tools such as genetically modified mice and intravital microscopy to the evaluation of molecular and cellular mechanisms of thrombosis. Among several unexpected findings of this approach was the discovery that protein disulfide isomerase serves an essential role in thrombus formation at sites of vascular injury. The observation that the commonly ingested quercetin flavonoid, quercetin-3-rutinoside, inhibits protein disulfide isomerase and blocks thrombus formation in preclinical studies has set the stage for clinical trials using protein disulfide isomerase antagonists as antithrombotics. Although the mechanisms by which protein disulfide isomerase facilitates platelet activation and fibrin formation have yet to be elucidated, protein disulfide isomerase antagonists are currently being developed as antithrombotics. This review will consider what is known about the role of protein disulfide isomerase in platelet accumulation and fibrin generation with a focus on pharmacological strategies for blocking protein disulfide isomerase activity in the context of thrombus formation. Potential indications and clinical trial design for testing the efficacy of protein disulfide isomerase inhibition to reduce the incidence of thrombosis will be considered.

KEYWORDS:

blood platelet; platelet inhibitors; thrombosis

PMID:
25104801
PMCID:
PMC4270882
DOI:
10.1161/ATVBAHA.114.303410
[Indexed for MEDLINE]
Free PMC Article

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