Individuals with type 2 diabetes are at a significantly higher risk for developing atherosclerosis, the narrowing of arteries that contributes to advanced cardiovascular disease. While the causes of accelerated atherosclerosis in diabetes are unclear, it is thought that elevated levels of platelets that are present in the bloodstream of diabetic individuals may play a role. Anti-platelet therapies reduce the risk of cardiovascular events in non-diabetics, but this approach is less effective in diabetic individuals for unknown reasons.
In a study published this week in the JCI, Andrew Murphy's lab at the Baker IDI Heart and Diabetes Institute investigated the link between hyperglycemia and enhanced platelet production. In mice, they found that low blood sugar levels trigger platelet production in the bone marrow through activation of a receptor known as RAGE, which is expressed on Kuppfer cells in the liver. They corroborated this finding in humans, showing that upregulation of signaling through the RAGE pathway correlated with increased platelet production individuals with type 2 diabetes. Moreover, in a mouse model of diabetes, long-term blockade of RAGE receptor signaling reduced platelet production as well as atherogenesis.
Future studies that focus on targets within this RAGE-mediated pathway may lead to the discovery of more effective anti-platelet therapies to reduce the risk of atherosclerosis and cardiovascular disease in diabetic individuals.
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TITLE: Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes
AUTHOR CONTACT:
Andrew Murphy
Baker IDI Heart and Diabetes Institute
andrew.murphy@bakeridi.edu.au
View this article at: http://www.jci.org/articles/view/92450?key=3e39ebb2c8957e5ff9b4
ACCOMPANYING COMMENTARY
TITLE: Sugar makes neutrophils RAGE: linking diabetes-associated hyperglycemia to thrombocytosis and platelet reactivity
AUTHOR CONTACT:
Wolfgang Bergmeier
University of North Carolina School of Medicine
bergmeie@email.unc.edu
View this article at: http://www.jci.org/articles/view/94494?key=f6bfd9f4e6a64b7f7844
Journal
Journal of Clinical Investigation