PMID- 22427378
OWN - NLM
STAT- MEDLINE
DCOM- 20120725
LR  - 20211021
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 61
IP  - 6
DP  - 2012 Jun
TI  - Platelet isoprostane overproduction in diabetic patients treated with aspirin.
PG  - 1626-32
LID - 10.2337/db11-1243 [doi]
AB  - Aspirin modestly influences cardiovascular events in patients with type 2 
      diabetes mellitus (T2DM), but the reason is unclear. The aim of the study was to 
      determine whether in T2DM patients aspirin enhances platelet isoprostanes, which 
      are eicosanoids with proaggregating properties derived from arachidonic acid 
      oxidation by platelet NOX2, the catalytic subunit of reduced NAD phosphate 
      oxidase. A cross-sectional study was performed comparing T2DM patients, treated 
      (n = 50) or not treated (n = 50) with 100 mg/day aspirin, with 100 nondiabetic 
      patients, matched for age, sex, atherosclerosis risk factors, and aspirin 
      treatment. A short-term (7 days) treatment with 100 mg/day aspirin also was 
      performed in 36 aspirin-free diabetic and nondiabetic patients. Higher platelet 
      recruitment, platelet isoprostane, and NOX2 activation was found in diabetic 
      versus nondiabetic patients and in aspirin-treated diabetic patients versus 
      nontreated patients (P < 0.001). Platelet thromboxane (Tx) A(2) (P < 0.001) was 
      inhibited in all aspirin-treated patients. In the interventional study, aspirin 
      similarly inhibited platelet TxA(2) in diabetic and nondiabetic patients (P < 
      0.001). Platelet recruitment, isoprostane levels, and NOX2 activation showed a 
      parallel increase in diabetic patients (P < 0.001) and no changes in nondiabetic 
      patients. These findings suggest that in aspirin-treated diabetic patients, 
      oxidative stress-mediated platelet isoprostane overproduction is associated with 
      enhanced platelet recruitment, an effect that mitigates aspirin-mediated TxA(2) 
      inhibition.
FAU - Cangemi, Roberto
AU  - Cangemi R
AD  - I Clinica Medica, Sapienza University of Rome, Rome, Italy.
FAU - Pignatelli, Pasquale
AU  - Pignatelli P
FAU - Carnevale, Roberto
AU  - Carnevale R
FAU - Nigro, Carmen
AU  - Nigro C
FAU - Proietti, Marco
AU  - Proietti M
FAU - Angelico, Francesco
AU  - Angelico F
FAU - Lauro, Davide
AU  - Lauro D
FAU - Basili, Stefania
AU  - Basili S
FAU - Violi, Francesco
AU  - Violi F
LA  - eng
SI  - ClinicalTrials.gov/NCT01250340
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120316
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Isoprostanes)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Thromboxanes)
RN  - EC 1.6.3.- (CYBB protein, human)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Aspirin/*pharmacology
MH  - Blood Platelets/cytology/*drug effects/metabolism
MH  - Cross-Sectional Studies
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Diabetes Mellitus, Type 2/blood/*metabolism
MH  - Female
MH  - Humans
MH  - Isoprostanes/*metabolism
MH  - Male
MH  - Membrane Glycoproteins/metabolism
MH  - Middle Aged
MH  - NADPH Oxidase 2
MH  - NADPH Oxidases/metabolism
MH  - Thromboxanes/*metabolism
PMC - PMC3357260
EDAT- 2012/03/20 06:00
MHDA- 2012/07/26 06:00
PMCR- 2013/06/01
CRDT- 2012/03/20 06:00
PHST- 2012/03/20 06:00 [entrez]
PHST- 2012/03/20 06:00 [pubmed]
PHST- 2012/07/26 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - db11-1243 [pii]
AID - 1243 [pii]
AID - 10.2337/db11-1243 [doi]
PST - ppublish
SO  - Diabetes. 2012 Jun;61(6):1626-32. doi: 10.2337/db11-1243. Epub 2012 Mar 16.