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 language | English |
|---|---|
| Pages (from-to) | 350-354 |
| Number of pages | 5 |
| Journal | Thrombosis Research |
| Volume | 130 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 2012 |
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Keywords
- Aspirin resistance
- Diabetes
- Oxidative stress
- Platelet inhibition
- Thromboxane
ASJC Scopus subject areas
- Hematology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus
AU - Ames, Paul R J
AU - Batuca, Joana R.
AU - Muncy, Ivana J.
AU - De La Torre, Ignacio Garcia
AU - Pascoe-Gonzales, Sara
AU - Guyer, K.
AU - Matsuura, Eiji
AU - Lopez, Luis R.
PY - 2012/9
Y1 - 2012/9
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.
AB - 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.
KW - Aspirin resistance
KW - Diabetes
KW - Oxidative stress
KW - Platelet inhibition
KW - Thromboxane
UR - http://www.scopus.com/inward/record.url?scp=84865260242&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865260242&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2012.03.025
DO - 10.1016/j.thromres.2012.03.025
M3 - Article
C2 - 22521214
AN - SCOPUS:84865260242
VL - 130
SP - 350
EP - 354
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 3
ER -