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, Eiji Matsuura, Luis R. Lopez

Research output: Contribution to journalArticle

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 2012

Fingerprint

Thromboxanes
Type 2 Diabetes Mellitus
Aspirin
Diabetes Mellitus
Oxidative Stress
Dinoprost
Selectins
Aryldialkylphosphatase
Cyclooxygenase 1
Platelet Activation
Creatinine
Blood Platelets
Nitrites
Oxidants
Nitrates
Eating
Biomarkers
Serum
11-dehydro-thromboxane B2

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Ames, P. R. J., Batuca, J. R., Muncy, I. J., De La Torre, I. G., Pascoe-Gonzales, S., Guyer, K., ... 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

Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus. / Ames, Paul R J; Batuca, Joana R.; Muncy, Ivana J.; De La Torre, Ignacio Garcia; Pascoe-Gonzales, Sara; Guyer, K.; Matsuura, Eiji; Lopez, Luis R.

In: Thrombosis Research, Vol. 130, No. 3, 09.2012, p. 350-354.

Research output: Contribution to journalArticle

Ames, PRJ, Batuca, JR, Muncy, IJ, De La Torre, IG, Pascoe-Gonzales, S, Guyer, K, Matsuura, E & Lopez, LR 2012, 'Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus', Thrombosis Research, vol. 130, no. 3, pp. 350-354. https://doi.org/10.1016/j.thromres.2012.03.025
Ames, Paul R J ; Batuca, Joana R. ; Muncy, Ivana J. ; De La Torre, Ignacio Garcia ; Pascoe-Gonzales, Sara ; Guyer, K. ; Matsuura, Eiji ; Lopez, Luis R. / Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus. In: Thrombosis Research. 2012 ; Vol. 130, No. 3. pp. 350-354.
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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.",
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AU - Pascoe-Gonzales, Sara

AU - Guyer, K.

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N2 - 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.

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KW - Aspirin resistance

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