Hyperglycemia enhances arsenic-induced platelet and megakaryocyte activation

Abstract

ObjectiveLow to moderate inorganic arsenic (iAs) exposure is independently associated with cardiovascular disease (CVD), particularly for patients with diabetes mellitus (DM). The mechanism of increased CVD risk from iAs exposure in DM has not been adequately characterized. We evaluated whether increasing concentrations of glucose enhance the effects of iAs on platelet and megakaryocyte activity, key steps in atherothrombosis.MethodsHealthy donor whole blood was prepared in a standard fashion and incubated with sodium arsenite in a range from 0 to 10 µM. iAs-induced platelet activation was assessed by platelet receptor CD62P (P-selectin) expression and monocyte-platelet and leukocyte-platelet aggregation (MPA and LPA, respectively) in the presence of increasing sodium arsenite and glucose concentrations. Megakaryocyte (Meg-01) cell adhesion and gene expression was assessed after incubation with or without iAs and increasing concentrations of d-glucose.ResultsPlatelet activity markers increased significantly with 10 vs. 0 µM iAs (P < 0.05 for all) and with higher d-glucose concentrations. Platelet activity increased significantly following co incubation of 1 and 5 µM iAs concentrations with hyperglycemic d-glucose (P < 0.01 for both) but not after incubation with euglycemic d-glucose. Megakaryocyte adhesion was more pronounced after co incubation with iAs and hyperglycemic than euglycemic d-glucose, while gene expression increased significantly to iAs only after co incubation with hyperglycemic d-glucose.ConclusionWe demonstrate that glucose concentrations common in DM potentiate the effect of inorganic arsenic exposure on markers of platelet and megakaryocyte activity. Our results support recent observational cohort data that DM enhances the vasculotoxic effects of arsenic exposure, and suggest that activation of the platelet-megakaryocyte hemostatic axis is a pathway through which inorganic arsenic confers atherothrombotic risk, particularly for patients with DM.

Antiplatelet Effects of Clopidogrel Vs Aspirin in Virologically Controlled HIV

“…All work was performed using the manufacturers’ protocols and as previously published. 29 , 30 Transcripts were normalized to the housekeeping gene RNA18S5 and are reported as fold change over control. All primers were obtained from Integrated DNA Technologies.…”

A brief review of the biology of megakaryocytes and platelets and their role in thrombosis associated with particulate air pollution

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“…These proteins then bind to their receptors on Kupffer cells for advanced glycation end products, triggering the production of IL-6, and causing hepatocytes to secrete TPO, which further leads to increased megakaryocyte proliferation and reticulated platelet production [ 54 , 55 ]. Another study reported that hyperglycemia can enhance sodium arsenite-induced megakaryocyte adhesion, platelet P-selectin expression, and leukocyte-platelet aggregation [ 56 ]. Megakaryocyte adhesion is often considered one of the markers of atherothrombosis risk [ 57 ].…”