Regulatory role of thiol isomerases in thrombus formation.

Abstract

INTRODUCTION:

The protein disulfide isomerase (PDI) family of thiol isomerases are intracellular enzymes known to catalyze the oxidation, reduction and isomerization of disulfide bonds during protein synthesis in the endoplasmic reticulum. PDI and related members of the thiol isomerase family are known to localize extracellularly where they possess various functions. Among these, the role of PDI in the initiation of thrombus formation is best characterized. PDI is secreted within seconds from activated platelets and endothelial cells at the site of vascular injury and accumulates in the developing platelet-fibrin thrombus. Inhibition of PDI by antibodies or small molecule inhibitors blocks thrombus formation. Efforts are underway to identify extracellular substrates of PDI that participate in the network pathways linking thiol isomerases to thrombus formation. ERp57, ERp5 and ERp72 also play a role in initiation of thrombus formation but their specific extracellular substrates are unknown. Areas covered: The following review gives an overview of biochemistry of vascular thiol isomerases followed by a detailed description of their role in thrombosis and its clinical implications. Expert commentary: The thiol isomerase system, by controlling the initiation of thrombus formation, provides the regulatory switch by which the normal vasculature is protected under physiologic conditions from thrombi generation.

• Authors: Anish Sharda, Bruce Furie
• Journal: Expert review of hematology (Expert Rev Hematol) Vol. 11 Issue 5 Pg. 437-448 (05 2018) ISSN: 1747-4094 [Electronic] England
• PMID: 29542339 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Fibrin
• Protein Disulfide-Isomerases

Topics

• Animals
• Blood Coagulation (physiology)
• Blood Platelets (cytology, metabolism)
• Fibrin (metabolism)
• Humans
• Platelet Activation (physiology)
• Protein Disulfide-Isomerases (metabolism)