Protein disulfide-isomerase (PDI) (PDI)

Platelet thiol-dependent mechanisms refer to the essential role of thiol-disulfide exchange reactions on the platelet surface in regulating haemostasis and thrombosis [2.2.1]. These reactions are primarily catalyzed by the enzyme Protein Disulfide-Isomerase (PDI), which is rapidly released from platelet granules and endothelial cells upon vascular injury [3.1.2, 3.2.3]. PDI catalyzes the rearrangement of disulfide bonds in key surface receptors, such as integrin alpha-IIb beta-3 (the fibrinogen receptor) and the P2Y12 receptor, which is a prerequisite for their activation and subsequent platelet aggregation [2.1.2, 2.2.1]. Targeting PDI with small molecules like isoquercetin has emerged as a promising antithrombotic strategy, particularly for cancer-associated thrombosis, as it inhibits thrombus formation with a potentially superior safety profile regarding bleeding compared to traditional antiplatelet agents [3.1.2, 3.1.4]. Clinical trials have demonstrated that oral isoquercetin can significantly reduce markers of hypercoagulability, such as D-dimer and thrombin generation, by inhibiting plasma PDI activity [3.1.2, 3.1.5].

Other names

P4HBPDIA1ERp59Prolyl 4-hydroxylase subunit betaPlatelet surface thiolsThiol isomerasePlatelet thiol-dependent mechanisms

Inhibition of extracellular protein disulfide-isomerase (PDI) activity on the platelet surface, preventing the reduction and isomerization of disulfide bonds in receptors such as integrin alpha-IIb beta-3 and P2Y12, thereby blocking platelet activation and aggregation [2.1.1, 3.1.3].