Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation.
Thromboxane (Tx) A2 is a platelet agonist, smooth muscle cell constrictor, and mitogen. Urinary Tx metabolite (Tx-M) excretion is increased in syndromes of platelet activation and early in both normal pregnancies and in pregnancy-induced hypertension. A further increment occurs in patients presenting with severe preeclampsia, in whom Tx-M correlates with other indices of disease severity. TxA2 exerts its effects through a membrane receptor (TP), of which two isoforms (alpha and beta; refs. 5,6) have been cloned. Overexpression of TP in the vasculature under the control of the pre-proendothelin-1 promoter 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 biosynthesis.
Rocca
B
B
The Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Loeb
A L
AL
Strauss
J F
JF
Vezza
R
R
Habib
A
A
Li
H
H
FitzGerald
G A
GA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D017482:Receptors, Thromboxane / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid