TY - JOUR
T1 - Dual inhibition of cyclooxygenase and lipoxygenase pathways by lipoproteins in human platelets
AU - Saeed, Sheikh Arshad
AU - Waqar, Muhammad Anwar
AU - Motiwala, Afaq
AU - Ali, Syed Umer
AU - Khan, Muhammad Umair
AU - Waqar, Muhammad Atif
AU - Ali, Rushna Parvez
PY - 2008/2
Y1 - 2008/2
N2 - 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 F1α (a stable metabolite of prostacyclin) in a concentration related manner All three lipoproteins also exerted an inhibitory influence on the biosynthesis of prostaglandin F 2α (PGF2α) 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.
AB - 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 F1α (a stable metabolite of prostacyclin) in a concentration related manner All three lipoproteins also exerted an inhibitory influence on the biosynthesis of prostaglandin F 2α (PGF2α) 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.
UR - http://www.scopus.com/inward/record.url?scp=79952010591&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:79952010591
SN - 0253-5106
VL - 30
SP - 119
EP - 125
JO - Journal of the Chemical Society of Pakistan
JF - Journal of the Chemical Society of Pakistan
IS - 1
ER -
