Platelet Cyclooxygenase Expression in Normal Dogs

Autor: C. Langston, Andrew J. Mackin, Lesya M. Pinchuk, K. Mullins, Stephen B. Pruett, Robert W. Wills, John V. Stokes, Kari V. Lunsford, Ron McLaughlin, John M. Thomason
Rok vydání: 2011
Předmět:
Zdroj: Journal of Veterinary Internal Medicine. 25:1106-1112
ISSN: 0891-6640
DOI: 10.1111/j.1939-1676.2011.00781.x
Popis: Background: Human platelets express both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Variation in COX-2 expression could be a mechanism for variable response to aspirin. Hypothesis/Objectives: The hypotheses were that circulating canine platelets express COX-1 and COX-2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs. Animals: Eight female, intact hounds. Methods: A single population, repeated measures design was used to evaluate platelet COX-1 and COX-2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA-100® (collagen/epinephrine), and urine 11-dehydro-thromboxane B2 (11-dTXB2) was measured and normalized to urinary creatinine. Differences in COX expression, PFA-100® closure times, and urine 11-dTXB2 : creatinine ratio were analyzed before and after aspirin administration. Results: Both COX-1 and COX-2 were expressed in canine platelets. COX-1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63–476%), while COX-2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA-100® closure times were prolonged and urine 11-dTXB2 concentration decreased in all dogs after aspirin administration. Conclusions and Clinical Importance: Canine platelets express both COX isoforms. After aspirin exposure, COX-1 expression increased despite impairment of platelet function, while COX-2 expression varied markedly among dogs. Variability in platelet COX-2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness.
Databáze: OpenAIRE