Abstract 15725: Reversal of Acute Hyperglycemia Restores Tissue Responsiveness to Nitric Oxide and Improves Endothelial Progenitor Cell Function Without Downregulating Platelet Thioredoxin Interacting Protein
Background: Hyperglycemia in acute coronary syndrome (ACS) is associated with substantial mortality. Rapid correction by IV insulin is associated with improvement in tissue responsiveness to nitric oxide (NO), reduction of superoxide content and improved prognosis. Upregulation of thioredoxin interacting protein (Txnip), a modulator of oxidative stress and of NO signaling by hyperglycemia is rapid, but little is known about the kinetics of its downregulation when this stimulus is removed. We therefore tested the hypothesis that correction of hyperglycemia (1) rapidly downregulates Txnip in platelets and (2) leads to (NO-mediated) improvements in endothelial progenitor cell (EPC) function.
Methods: Patients were recruited on the basis of ACS and severe hyperglycemia. Investigations performed before and 12 hours post initiation of insulin infusion: platelet responsiveness to anti-aggregatory effect of NO donor sodium nitroprusside (via whole blood aggregometry), whole blood total reactive oxygen species (ROS) content (via EPR), platelet Txnip content (via immunohistochemistry), CD34/133 count (via flow cytometry), and EPC function (via colony forming units [CFU]).
Results: Patients (n=12) were aged 66 ± 11 (SD): Blood glucose level fell from median of 15 to 7mmol/L (p<0.001) over 12 hours. Key effects observed were as shown in Table 1:
Conclusion: 1.While these data confirm that correction of hyperglycemia in ACS rapidly sensitises platelets to NO and reduces ROS generation, these effects appear to be Txnip-independent.
2.Simultaneously, EPC function (but not numbers) improve, consistent also with increased NO effect.
- © 2013 by American Heart Association, Inc.