Dual inhibition of cyclooxygenase and lipoxygenase pathways by lipoproteins in human platelets

Sheikh Arshad Saeed, Muhammad Anwar Waqar, Afaq Motiwala, Syed Umer Ali, Muhammad Umair Khan, Muhammad Atif Waqar, Rushna Parvez Ali

Research output: Contribution to journalArticle

Abstract

Products of arachidonic acid (AA) metabolism i.e., prostaglandins (PGs), prostacyclin (PGI2), thromboxane-A2 (TXA2) and lipoxygenase metabolites serve important roles in the pathogenesis of ischaemic heart disease and thrombosis. In the present study, we investigated the effects of lipoproteins on the products of AA metabolism produced by bovine seminal vesicles (BSV) and human blood platelets. Lipoproteins were separated by density gradient zonal ultracentrifugation and their effects on the synthesis of various AA metabolites were measured using radioimmunoassays. The results show that human lipoproteins VLDL, LDL and HDL inhibited AA metabolism to varying extents. VLDL, LDL and HDL inhibited the biosynthesis of prostaglandin E 2 and 6-ketoprostagladin F (a stable metabolite of prostacyclin) in a concentration related manner All three lipoproteins also exerted an inhibitory influence on the biosynthesis of prostaglandin F (PGF) although not in a concentration-related manner. The effects of lipoproteins on the production of AA metabolites by human platelets i.e. TXA2 and 12-hydroxy- eicosatetraenoic acids (12-HETEs) were also studied using radiometric thin layer chromatography coupled with automated data integrator system. In human platelets, HDL had a concentration-dependent inhibitory effect on the production of 12-HETE and TXA2, whereas, LDL had a strong inhibitory effect on TXA2 production but weakly inhibited the production of 12-HETE. In contrast, VLDL did not exhibit any effect on AA metabolism by platelets. These results demonstrate an hitherto unrecognized property of human lipoproteins and point to a new facet of lipoprotein action.

Original languageEnglish (US)
Pages (from-to)119-125
Number of pages7
JournalJournal of the Chemical Society of Pakistan
Volume30
Issue number1
StatePublished - Feb 2008
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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    Saeed, S. A., Waqar, M. A., Motiwala, A., Ali, S. U., Khan, M. U., Waqar, M. A., & Ali, R. P. (2008). Dual inhibition of cyclooxygenase and lipoxygenase pathways by lipoproteins in human platelets. Journal of the Chemical Society of Pakistan, 30(1), 119-125.