Thromboxane A2 Generation, in the Absence of Platelet COX-1 Activity, in Patients With and Without Atherothrombotic Myocardial Infarction

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概要

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• 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). Methods and 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 ≥1mmol/L arachidonic acid. Median urine 11-dehydro-TxB2 was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244pg/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. 606pg/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.

著者

• Blumenthal Roger

  Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, Department of Medicine

• Jaffe Allan

  Mayo Clinic, Mayo Clinic and Medical School

• Gerstenblith Gary

  Johns Hopkins University School of Medicine, Johns Hopkins Hospital

• Saenger Amy

  Mayo Clinic, Mayo Clinic and Medical School

• DeFilippis Andrew

  University of Louisville, Rudd Heart and Lung Center/Kentucky One Health and Johns Hopkins Ciccarone Center for the Prevention of Heart Disease

• Oloyede Oluwasegun

  Johns Hopkins Bloomberg School of Public Health

• Andrikopoulou Efstathia

  Thomas Jefferson University Hospitals

• Palachuvattil Joel

  Johns Hopkins Bloomberg School of Public Health

• Fasoro Yetunde

  Johns Hopkins Bloomberg School of Public Health

• Guallar Eliseo

  Johns Hopkins Bloomberg School of Public Health

• Kickler Thomas

  Johns Hopkins University School of Medicine, Johns Hopkins Hospital

• Schulman Steven

  Johns Hopkins University School of Medicine, Johns Hopkins Hospital

• Rade Jeffrey

  University of Massachusetts, UMASS Medical School

関連論文

• PE-411 NCEP III Guidelines Performance in a Large Cohort without a History of Coronary Artery Disease : KAMIR Study(PE069,Preventive Medicine/Epidemiology/Education 2 (H),Poster Session (English),The 73rd Annual Scientific Meeting of the Japanese Circulat
• Thromboxane A2 Generation, in the Absence of Platelet COX-1 Activity, in Patients With and Without Atherothrombotic Myocardial Infarction

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