Modulation of rat platelet activation by vessel wall-derived prostaglandin and platelet-derived thromboxane: effects of dietary fish oil on thromboxane-prostaglandin balance

C.M.A. Nieuwenhuys, M.A.H. Feijge, R. Offermans, A.D.M. Kester, G. Hornstra, J.W.M. Heemskerk

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Modulation of rat platelet activation by vessel wall-derived prostaglandin and platelet-derived thromboxane: effects of dietary fish oil on thromboxane-prostaglandin balance.

Nieuwenhuys CM, Feijge MA, Offermans RF, Kester AD, Hornstra G, Heemskerk JW.

Department of Human Biology, University of Maastricht, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

By dietary manipulation of rats with n-3 polyunsaturated fatty acids (PUFAs), platelets and endothelium-containing aortic tissue were obtained with decreased levels of arachidonate and increased levels of eicosapentaenoate and docosahexaenoate. These diet-induced changes were accompanied by a reduced formation of thromboxane A(2) (TXA(2)) and prostaglandin I(2) (PGI(2)) in platelets and aortic tissue, respectively. When platelets were incubated with autologous, aorta-derived PGI(2), the dietary modulation of PGI(2) generation had a stronger effect on the activation process than the dietary effect on TXA(2) generation. The platelet-inhibiting effect of PGI(2) was independent of the type of agonist and involved both TXA(2)-dependent and -independent activation responses. PGI(2) also inhibited the agonist-induced formation of TXA(2). In addition, the platelet-inhibitory effect of PGI(2) was more prolonged in time than the brief, stimulatory effect of TXA(2). We conclude that, in the thromboxane-prostaglandin balance of platelet activation, PGI(2) plays a more prominent role than TXA(2). Furthermore, dietary n-3 PUFAs appear to influence platelet activation more by reducing formation of endothelial PGI(2) than by decreasing autocrine-produced TXA(2). Thus, in rats, the proposed antithrombotic effect of fish oil is unlikely to be caused by an altered thromboxane-prostaglandin balance.
Original languageEnglish
Pages (from-to)355-366
Number of pages12
JournalAtherosclerosis
Volume154
DOIs
Publication statusPublished - 1 Jan 2001

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