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Picking prostanoids to provide protection

16.09.2004


Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice



Atherosclerosis is an inflammation in the lining of the arteries. Biological chemicals in the body called pros-tanoids, which are made from the breakdown of arachidonic acid by the action of an enzyme called COX have been implicated in the development of atherosclerosis. The role of prostanoids in inflammation is well known, based on studies of aspirin-like non-steroidal anti-inflammatory drugs, which act to inhibit the action of COX. Two prostenoids called PG I2/prostacyclin (PGI2) and thromboxane A2 (TXA2), are ele-vated in individuals with atheroscle-rosis, but their roles in the initiation and development of atherosclerosis remain ill-defined. To investigate the role of each of these prostanoids in atherosclerosis, Shuh Narumiya and colleagues, of Kyoto University Faculty of Medicine, have bred an ath-erosclerotic mouse model (apoE–/–) with mice that were deficient in either the PGI receptor (IP) or the TXA receptor (TP).

These mice allowed the authors to examine the effect of loss of PGI or TXA action on atherosclerosis development. Relative to apoE–/– mice, the apoE–/–IP–/– mice had accelerated initiation and development of athero-sclerosis, while the apoE–/–TP–/– mice had delayed development. apoE–/–IP–/– mice also demonstrated other mark-ers of more severe disease, compared with apoE–/– mice. apoE–/–TP–/– mice presented with fewer markers of dis-ease. These data indicate that PGI2 protects against and TXA2 promotes atherosclerosis development. The use of TP antagonists and molecules with PG-like activity may therefore aid in atherosclerosis prevention. Furthermore these data fit well with previous work that indicated that low doses of aspirin, which inhibits TXA2 more than PGI2, has been used as anti-platelet therapy for the prevention of myocardial infarction and recurrence of strokes.

Laurie Goodman | EurekAlert!
Further information:
http://www.jci.org

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