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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3291-3296. Prepublished online as a Blood First Edition Paper on December 7, 2006; DOI 10.1182/blood-2006-08-044990. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-044990v1 109/8/3291    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cyrus, T. Articles by Praticò, D. Search for Related Content PubMed PubMed Citation Articles by Cyrus, T. Articles by Praticò, D. Related Collections Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thromboxane receptor blockade improves the antiatherogenic effect of thromboxane A2 suppression in LDLR KO mice Tillmann Cyrus2, Yuemang Yao1, Tao Ding1, Jean Michel Dogné3, and Domenico Praticò1 1 Department of Pharmacology, University of Pennsylvania, Philadelphia; 2 Division of Cardiology, Washington University, St Louis, MO; 3 Department of Pharmacy, University of Namur, Belgium Suppression of thromboxane (Tx) A2 biosynthesis retards atherogenesis. In this setting, the coincidental presence of nonconventional ligands for the TxA2 receptor (TP), such as isoprostanes, could still induce a proatherogenic vascular phenotype. However, no data are available on the effect of combining suppression of TxA2 formation with blockade of TP in atherogenesis. To this end, we tested the effect of a selective COX-1 inhibitor, SC560, a TP antagonist, BM-573, or a combination of both in low-density lipoprotein receptor-deficient mice on a high-fat diet. None of the treatments affected body weight or plasma cholesterol or triglycerides levels. Although SC-560 suppressed TxA2 biosynthesis, BM-573 reduced its levels by 35%; in contrast, the 2 drugs, alone or in combination, did not significantly affect prostacyclin levels. At the end of the study, SC560 and BM-573 reduced atherogenesis; however, a further significant decrease was observed in mice receiving both drugs. This effect was associated with a further significant reduction of vascular inflammation, a decrease in macrophages, and an increase in the content of collagen and smooth muscle cells of the atherosclerotic lesions. These results show for the first time that the addition of a TP antagonist increases the antiatherogenic effect of COX-1–dependent TxA2 suppression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-E. Gendron and E. Thorin A change in the redox environment and thromboxane A2 production precede endothelial dysfunction in mice Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2508 - H2515. [Abstract] [Full Text] [PDF]

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