title: Fatty acids and TxA(2) generation, in the absence of platelet-COX-1 activity.
abstract: OBJECTIVE
  Omega-3 fatty acids suppress Thromboxane A(2) (TxA(2)) generation via mechanisms independent to that of aspirin therapy. We sought to evaluate whether baseline omega-3 fatty acid levels influence arachidonic acid proven platelet-cyclooxygenase-1 (COX-1) independent TxA(2) generation (TxA(2) generation despite adequate aspirin use).
  
  
  RESULTS
  Subjects with acute myocardial infarction, stable CVD or at high risk for CVD, on adequate aspirin therapy were included in this study. Adequate aspirin action was defined as complete inhibition of platelet-COX-1 activity as assessed by <10% change in light transmission aggregometry to ≥1 mmol/L arachidonic acid. TxA(2) production was measured via liquid chromatography-tandem mass spectrometry for the stable TxA(2) metabolite 11-dehydro-thromboxane B2 (UTxB2) in urine. The relationship between baseline fatty acids, demographics and UTxB(2) were evaluated. Baseline omega-3 fatty acid levels were not associated with UTxB(2) concentration. However, smoking was associated with UTxB(2) in this study.
  
  
  CONCLUSIONS
  Baseline omega-3 fatty acid levels do not influence TxA(2) generation in patients with or at high risk for CVD receiving adequate aspirin therapy. The association of smoking and TxA(2) generation, in the absence of platelet COX-1 activity, among aspirin treated patients warrants further study.
authors.affiliation: University of Louisville, Rudd Heart & Lung Center/Kentucky One Health, Louisville, KY, USA; The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. Electronic address: apdefi01@louisville.edu.
authors.forename: A P
authors.initials: AP
authors.lastname: DeFilippis
authors.affiliation: Biostatistics Shared Facility, JG Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Rai
authors.affiliation: Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cambon
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Miles
authors.affiliation: Cardiovascular division, Mayo Clinic, Rochester, MN, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Jaffe
authors.affiliation: The Hugo W. Moser Research Institute, The Kennedy Krieger Institute, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Moser
authors.affiliation: The Hugo W. Moser Research Institute, The Kennedy Krieger Institute, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: R O
authors.initials: RO
authors.lastname: Jones
authors.affiliation: Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bolli
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Schulman
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D002853:Chromatography, Liquid; D051545:Cyclooxygenase 1 / Q000097:blood*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D012907:Smoking / Q000009:adverse effects / Q000097:blood / Q000652:urine; D053719:Tandem Mass Spectrometry; D013928:Thromboxane A2 / Q000097:blood*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D015525:Fatty Acids, Omega-3; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin
keywords: Aspirin resistance; Omega-3 fatty acids; Platelet activation; Smoking; Thromboxane