Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus

Paul R.J. Ames, Joana R. Batuca, Ivana J. Muncy, Ignacio Garcia De La Torre, Sara Pascoe-Gonzales, K. Guyer, E. Matsuura, Luis R. Lopez

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20 Citations (Scopus)

Abstract

Introduction: Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on platelet activation, thromboxane generation, oxidative stress and anti-oxidant biomarkers was studied in type 2 diabetes mellitus (DM). Material and methods: Baseline and post-ASA samples (100/325 mg x 7 days) were obtained from 75 DM patients and 86 healthy controls for urinary 11-dehydro-thromboxane B2 (11dhTxB2), 8-iso-prostaglandin-F2α (8-isoPGF2α) and serum sP-Selectin, nitrite (NO2-), nitrate (NO3-) and paraoxonase 1 (PON1) activity. Results: Compared to baseline controls, baseline DM had higher mean levels of 11dhTxB2 (3,665 ± 2,465 vs 2,450 ± 1,572 pg/mg creatinine, p = 0.002), 8-isoPGF2α (1,457 ± 543 vs 1,009 ± 412 pg/mg creatinine, p < 0.0001), NO2- (11.8 ± 7.3 vs 4.8 ± 5.3 μM, p < 0.0001), NO3- (50.4 ± 39.3 vs 20.9 ± 16.7 μM, p < 0.0001) and sP-Selectin (120.8 ± 56.7 vs 93.0 ± 26.1 ng/mL, p = 0.02), and the same held for post-ASA levels (p < 0.0001). ASA demonstrated no effect on 8-isoPGF2α, NO2 -, NO3-, sP-Selectin or PON1 activity in either DM or controls. Post ASA inhibition of urinary 11dhTxB2 was 71.5% in DM and 75.1% in controls. There were twice as many ASA poor responders in DM than in controls (14.8% and 8.4%) based on systemic thromboxane reduction. Urinary 8-isoPGF2α excretion was greater in DM ASA poor responders than good responders (p < 0.009). Conclusions: This suggests that oxidative stress may maintain platelet function irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.

Original languageEnglish
Pages (from-to)350-354
Number of pages5
JournalThrombosis Research
Volume130
Issue number3
DOIs
Publication statusPublished - Sep 1 2012

Keywords

  • Aspirin resistance
  • Diabetes
  • Oxidative stress
  • Platelet inhibition
  • Thromboxane

ASJC Scopus subject areas

  • Hematology

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    Ames, P. R. J., Batuca, J. R., Muncy, I. J., De La Torre, I. G., Pascoe-Gonzales, S., Guyer, K., Matsuura, E., & Lopez, L. R. (2012). Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus. Thrombosis Research, 130(3), 350-354. https://doi.org/10.1016/j.thromres.2012.03.025