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Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation

Nature Medicine volume 6, pages 219–221 (2000)Cite this article

Abstract

Thromboxane (Tx) A2 is a platelet agonist, smooth muscle cell constrictor, and mitogen1. Urinary Tx metabolite (Tx-M) excretion is increased in syndromes of platelet activation and early in both normal pregnancies and in pregnancy-induced hypertension2,3. A further increment occurs in patients presenting with severe preeclampsia, in whom Tx-M correlates with other indices of disease severity4. TxA2 exerts its effects through a membrane receptor (TP), of which two isoforms (α and β; refs. 5,6) have been cloned. Overexpression of TP in the vasculature under the control of the pre-proendothelin-1 promoter7 results in a murine model of intrauterine growth retardation (IUGR), which is rescued by timed suppression of Tx synthesis with indomethacin. IUGR is commonly associated with maternal diabetes or cigarette smoking, both conditions associated with increased TxA2 biosynthesis8,9.

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Figure 1: a, MSAP responses of anesthetized wild-type (⋄) (n=5 per dose) and TP+/+ (▪) (n=3–5 per dose) mice to different doses of U-46619 were measured by carotid artery catheterization.
Figure 2: Embryos were isolated from TP+/+ and wild-type females mated with wild-type males at gestational day 11.5 (a) and 13.5 (b).
Figure 3: Placentas were isolated from TP+/+ and wild-type females at gestational day 11.5 (a) and 13.5 (b).

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Acknowledgements

This work was supported by grants from the National Institutes of Health (HL 54500, HL 57847 and HD 29946) and an American Heart Association (Mid-Atlantic Research Consortium) grant-in-aid. G.A.F. is the Robinette Foundation Professor of Cardiovascular Medicine.

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Authors and Affiliations

  1. The Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania

    Bianca Rocca, Alex L. Loeb, Roberta Vezza, Aida Habib, Hongwei Li & Garret A. FitzGerald

  2. The Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania

    Jerome F. Strauss III

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  1. Bianca Rocca
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Correspondence to Garret A. FitzGerald.

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Rocca, B., Loeb, A., Strauss, J. et al. Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation. Nat Med 6, 219–221 (2000). https://doi.org/10.1038/72334

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