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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 (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 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 Pratico, D. Search for Related Content PubMed PubMed Citation Articles by Cyrus, T. Articles by Pratico, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 31, 2006 Accepted November 30, 2006 Thromboxane receptor blockade improves the anti-atherogenic effect of thromboxane A2 suppression in LDLR KO mice Tillmann Cyrus, Yuemang Yao, Tao Ding, Jean Michel Dogne, and Domenico Pratico* Division of Cardiology, Washington University, Saint Louis, MO, United States Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, United States Department of Pharmacy, University of Namur, Namur, Belgium * Corresponding author; email: domenico{at}spirit.gcrc.upenn.edu. 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 pro-atherogenic 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. All treatments did not affect body weight, plasma cholesterol or triglycerides levels. While SC-560 suppressed TxA2 biosynthesis, BM-573 reduced its levels by 35%; by contrast, the two 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 collagen and smooth muscle cells content of the atherosclerotic lesions. These results show for the first time that the addition of a TP antagonist increases the anti-atherogenic 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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