Role of Prostacyclin in the Cardiovascular Response to Thromboxane A 2

American Association for the Advancement of Science (AAAS) - Tập 296 Số 5567 - Trang 539-541 - 2002
Yan Cheng1, Sandra Austin1, Bianca Rocca1, Beverly H. Koller2, Thomas M. Coffman3, Tilo Großer1, John A. Lawson1, Garret A. FitzGerald1
1Center for Experimental Therapeutics, 153 Johnson Pavilion, 3620 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA.
2Department of Medicine, University of North Carolina, Chapel Hill, NC 27559, USA.
3Department of Medicine, Duke University, Durham, NC 27705, USA.

Tóm tắt

Thromboxane (Tx) A 2 is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA 2 formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI 2 ) is a vasodilator that inhibits platelet function. Here we show that injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the PGI 2 receptor (IP) but are depressed in mice genetically deficient in the TxA 2 receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI 2 modulates platelet-vascular interactions in vivo and specifically limits the response to TxA 2 . This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), inhibit PGI 2 but not TxA 2 .

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Tài liệu tham khảo

10.1038/263663a0

10.1016/0090-6980(76)90125-8

10.1056/NEJM198404263101701

10.1056/NEJM200108093450607

10.1073/pnas.96.1.272

Catella-Lawson F., et al., J. Pharm. Exp. Ther. 289, 735 (1999).

10.1073/pnas.93.19.10417

10.1074/jbc.M100429200

10.1056/NEJM200011233432103

10.1016/S0021-9258(17)36979-X

10.1038/349617a0

10.1038/41780

10.1172/JCI5116

W. M. Cheung M. R. D'Andrea

10.1161/01.ATV.19.12.3014

Supplementary material is available on Science Online at www.sciencemag.org/cgi/content/full/296/5567/539/DC1.

10.1161/01.CIR.84.2.679

10.1056/NEJM198806303182603

10.1016/S0960-894X(98)00220-0

10.1038/72334

Y. Cheng G. A. FitzGerald unpublished observations.

Pedersen M. L., Watson M., FitzGerald G. A., Thromb. Res. 35, 99 (1983).

10.1016/0002-9149(91)90379-Y

10.1161/01.CIR.71.3.434

10.1016/0049-3848(84)90213-5

10.1172/JCI109967

10.1172/JCI113895

10.1172/JCI2592

10.1074/jbc.M010606200

10.1016/S0021-9258(18)45792-4

10.1074/jbc.M907881199

10.1378/chest.119.1_suppl.39S

10.1161/01.CIR.84.4.1568

10.1161/01.CIR.92.11.3194

We wish to thank P. McNamara and R. D. Rudic for advice and encouragement. We also thank S. Segel and H. Li for technical assistance. Supported in part by grants from Servier and the National Institutes of Health (HL 54500 and HL 62250). All procedures were considered and approved by Institutional Animal Care and Usage Committee of the University of Pennsylvania.

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American Association for the Advancement of Science (AAAS)

Tập 296 Số 5567

539-541

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