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Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA, ingrid.avalos{at}vanderbilt.edu

Cecilia P. Chung

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

Annette Oeser

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

Ginger L. Milne

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

Holly Borntrager

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

Jason D. Morrow

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

Paolo Raggi

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA

Joseph Solus

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

C. Michael Stein

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

Incomplete suppression of thromboxane biosynthesis during aspirin therapy is associated with increased cardiovascular risk. Since systemic lupus erythematosus (SLE) is associated with platelet activation and increased cardiovascular mortality, we compared thromboxane and prostacyclin biosynthesis in patients with SLE and control subjects, and measured inhibition of thromboxane excretion in aspirin-treated subjects. We measured the urinary excretion of 11-dehydro thromboxane B ₂ (TXB₂) and 2,3-dinor 6-ketoPGF₁ (PGI-M), the stable metabolites of thromboxane A₂ and prostacyclin, respectively, in 74 patients with SLE and 70 controls. In subjects who were not receiving aspirin, TXB₂ excretion was higher in patients with SLE [0.40 ng/mg creatinine (0.26—0.64), median (interquartile range)] than controls [0.31 ng/mg creatinine (0.23—0.44)] (P = 0.04), and in these patients, TXB₂ excretion correlated with disease activity (rho = 0.28, P = 0.03) and tumor necrosis factor alpha (rho = 0.48, P < 0.001). Aspirin therapy resulted in significantly lower TXB₂ excretion in controls (P = 0.01), but not in patients with SLE (P = 0.10), compared with subjects not receiving aspirin. Prostacyclin biosynthesis did not differ among patients and controls, and was not affected by aspirin (P all >0.35). Thromboxane biosynthesis is increased in SLE and is associated with disease activity. Additionally, response to aspirin may be attenuated in some patients with SLE. Lupus (2007) 16, 981—986.

Key Words: systemic lupus erythematosus • asprin resistance • thromboxane • prostacyclin • oxidative stress

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Lupus, Vol. 16, No. 12, 981-986 (2007)
DOI: 10.1177/0961203307083313


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Avalos, I. Articles by Stein, C. M. Search for Related Content PubMed PubMed Citation Articles by Avalos, I. Articles by Stein, C. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLSALICYLIC ACID Medline Plus Health Information Lupus Social Bookmarking                         What's this?