Sugar makes neutrophils RAGE: linking diabetes-associated hyperglycemia to thrombocytosis and platelet reactivity

The Journal of Clinical Investigation
Robert H Lee, Wolfgang Bergmeier

Abstract

Diabetes mellitus is associated with an increased risk for cardiovascular disease, but the link between hyperglycemia and atherothrombotic disease is not completely understood. Patients with diabetes often show hyporesponsiveness to antiplatelet therapies, and it has been suggested that hyperreactive reticulated platelets underlie this altered therapeutic response. In this issue of the JCI, Kraakman et al. uncover a previously unknown link between hyperglycemia and enhanced platelet production and reactivity. The authors demonstrate that high blood glucose levels trigger neutrophil release of S100 calcium-binding protein A8/A9 (S100A8/A9), which binds to the receptor for advanced glycation end products (RAGE) on Kupffer cells, ultimately leading to increased thrombopoietin (TPO) production in the liver. TPO causes megakaryocyte proliferation and increased platelet production. This study demonstrates the importance of glycemic control and identifies potential therapeutic targets in the normalization of platelet numbers and function in diabetes.

References

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Citations

Nov 9, 2018·Platelets·Steve P Watson, Amanda Dalby
Jun 4, 2019·Medicina·Fatih TemizHakan Güneş
Sep 19, 2019·Journal of the Endocrine Society·Kamyar Asadipooya, Edilfavia Mae Uy
Jun 3, 2018·World Journal of Pediatrics : WJP·Anna MedkovaVladimir Mihal
Nov 27, 2019·European Journal of Preventive Cardiology·Bianca RoccaFrancesco Zaccardi
Dec 30, 2020·International Journal of Molecular Sciences·Lei Wang, Chaojun Tang
Jun 3, 2021·International Journal of Molecular Sciences·Catherine M DavisNabil J Alkayed

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