Hyperglycemia enhances arsenic-induced platelet and megakaryocyte activation.
Authors Newman JD, Echagarruga CT, Ogando YM, Montenont E, Chen Y, Fisher EA, Berger JS
Submitted By Jonathan Newman on 4/3/2017
Status Published
Journal Journal of translational medicine
Year 2017
Date Published 3/1/2017
Volume : Pages 15 : 55
PubMed Reference 28264687
Abstract Low 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., Healthy 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., Platelet 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., We
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.