title: Thromboxane A(2) generation, in the absence of platelet COX-1 activity, in patients with and without atherothrombotic myocardial infarction.
abstract: BACKGROUND
  Aspirin's therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI).
  
  
  RESULTS
  TxA2 production, in the absence of platelet COX-1 activity, was evaluated in 44 patients taking aspirin on 3 commercially available assays that detect metabolites of TxA2 in the urine. Two assays measure urine 11-dehydro-thromboxane B2 (TxB2) alone and 1 measures urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2. Platelet COX-1 inhibition was confirmed on <10% platelet aggregation in response to ≥1 mmol/L arachidonic acid. Median urine 11-dehydro-TxB2 was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311 pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244 pg/mg creatinine, P=0.11 via LC-MS/MS). Median urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2, however, was higher in those with vs. those without a diagnosis of atherothrombotic MI (1,035 vs. 606 pg/mg creatinine, P=0.03 via monoclonal ELISA).
  
  
  CONCLUSIONS
  Differences in TxA2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA2 generation was assessed on 11-dehydro-TxB2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA2 generation was assessed using 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA2 generation and suggest that 11-dehydro-2,3-dinor-TxB2 may be critical to the biology of atherothrombosis.
authors.affiliation: University of Louisville, Rudd Heart and Lung Center/Kentucky One Health and Johns Hopkins Ciccarone Center for the Prevention of Heart Disease.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: DeFilippis
authors.forename: Oluwasegun S
authors.initials: OS
authors.lastname: Oloyede
authors.forename: Efstathia
authors.initials: E
authors.lastname: Andrikopoulou
authors.forename: Amy K
authors.initials: AK
authors.lastname: Saenger
authors.forename: Joel M
authors.initials: JM
authors.lastname: Palachuvattil
authors.forename: Yetunde A
authors.initials: YA
authors.lastname: Fasoro
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kickler
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
authors.forename: Gary
authors.initials: G
authors.lastname: Gerstenblith
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schulman
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Rade
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000201:enzymology*; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000652:urine; D010974:Platelet Aggregation / Q000187:drug effects; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy / Q000652:urine; D013928:Thromboxane A2 / Q000097:blood* / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine
chemical_list: D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin