Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis

Ahmed, Niaz S. and Lopes-Pires, Maria E. and Pugh, Nicholas (2020) Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis. Platelets. ISSN 1369-1635

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Official URL: https://doi.org/10.1080/09537104.2020.1840540

Abstract

Zinc (Zn2+) is an essential micronutrient and the second most abundant trace metal in the human body. The important role that Zn2+ plays in hemostasis is exemplified by platelet-related bleeding phenotypes coinciding with dietary Zn2+ deficiency. These phenotypes are rectified upon Zn2+ supplementation. Labile (unbound) Zn2+ is present in the plasma at micromolar levels, but is also detected in atherosclerotic plaques, and released from platelet α granules. Therefore, it is likely that localized Zn2+ concentrations are higher at sites of thrombosis and hemostasis. Exogenous Zn2+ is a regulator of the hemostatic responses, with roles during coagulation and platelet activation. Extracellular Zn2+ gains access to the platelet cytosol and induces full platelet activation at high concentrations, and potentiates platelets to activation by conventional agonists at lower concentrations. Zn2+-induced platelet activation is dependent on PKC and integrin αIIbβ3, and is associated with tyrosine phosphorylation of platelet proteins. Agonist evoked platelet activation results in intracellular Zn2+ ([Zn2+]i) fluctuations that are sensitive to the platelet redox state. Increases in [Zn2+]i correlate with activation responses, including shape change, granule release, αIIbβ3 activation and phosphatidyl-serine exposure, consistent with a role as a second messenger. This review provides insight into the numerous demonstrated and potential roles for Zn2+ in platelet function during thrombosis and hemostasis, highlighting its increasing acceptance as an intracellular and extracellular platelet regulatory agent.

Item Type: Journal Article
Keywords: Platelets, Zinc, Thrombosis, Hemostasis, Second Messenger
Faculty: Faculty of Science & Engineering
Depositing User: Lisa Blanshard
Date Deposited: 18 Mar 2021 15:10
Last Modified: 18 Mar 2021 16:04
URI: https://arro.anglia.ac.uk/id/eprint/706427

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