Abstract 12412: Platelet Isoprostane Over-Production Enhances Platelet Function in Diabetic Patients Treated with Aspirin
Background- Aspirin modestly influences cardiovascular events in type 2 diabetic (T2DM) patients but the reason is unclear. We investigated whether in T2DM patients aspirin enhances platelet isoprostanes, which are eicosanoids with pro-aggregating properties derived from arachidonic acid oxidation by platelet NADPH oxidase.
Methods and Results- A cross-sectional study was performed in T2DM patients, treated (n=50) or not (n=50) with 100 mg/d aspirin. One hundred non-diabetic patients, matched for age, sex, atherosclerosis risk factors and aspirin treatment were enrolled as controls. A short-term (7 days) treatment with 100 mg/day aspirin was performed in 36 aspirin-free diabetic and non-diabetic patients, matched for sex, age, and atherosclerotic risk factors. Platelet recruitment, which mimics the propagation of aggregation and is dependent upon isoprostanes, platelet thromboxane (Tx) A2, platelet isoprostanes and platelet NOX2, the catalytic subunit of NADPH oxidase, were determined. Patients with diabetes had higher platelet recruitment, isoprostane levels, and NOX2 activation compared to non-diabetic patients (p<0.001). Aspirin-treated diabetic patients showed greater TxA2 inhibition, higher platelet recruitment, increased isoprostane, and greater NOX2 activation compared to non-treated diabetic patients (p<0.001). In non-diabetic patients, aspirin inhibited TxA2 (p<0.001) without affecting recruitment, isoprostane level, or NOX2 activation compared to aspirin-untreated controls. In the interventional study, aspirin similarly inhibited platelet TxA2 in diabetic and non-diabetic patients (p<0.001). Platelet recruitment, isoprostane level, and NOX2 activation showed a parallel increase in diabetic patients (p<0.001) but no change in non-diabetics.
Conclusion- In aspirin-treated diabetic patients, oxidative stress-mediated platelet isoprostane over-production is associated with enhanced platelet recruitment, an effect that mitigates TxA2 inhibition.
- © 2011 by American Heart Association, Inc.