Cyclic AMP regulation of endothelial cell triacylglycerol turnover, 13-hydroxyoctadecadienoic acid (13-HODE) synthesis and endothelial cell thrombogenicity.
The 15-omega-lipoxygenase enzyme in endothelial cells metabolizes endogenous linoleic acid (18:2) into 13-hydroxyoctadecadienoic acid (13-HODE) under basal conditions, i.e., in unstimulated endothelial cells. 13-HODE is thought to regulate the non-adhesivity of the endothelium, contributing to vessel wall/blood cell biocompatibility. We performed experiments, therefore, to determine the relationship between basal levels of cAMP, 13-HODE synthesis, and platelet/endothelial cell adhesion. We found that 13-HODE synthesis increased with elevated cAMP levels and that the elevated 13-HODE levels correlated with increased 18:2 turnover in the triacylglycerol pool. In contrast, neither 18:2 nor arachidonic acid (20:4) turnover in the phospholipid nor prostacyclin (PGI2) production were changed with elevated cAMP levels. Platelet/endothelial cell adhesion was inversely proportional to 13-HODE synthesis. We conclude that intracellular 13-HODE influences platelet/vessel wall interactions, is synthesized from 18:2 released from the endogenous triacylglycerol pool, and that this pathway is modulated by intracellular cAMP levels.
Haas
T A
TA
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Bertomeu
M C
MC
Bastida
E
E
Buchanan
M R
MR
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D000242:Cyclic AMP / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D013927:Thrombosis / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D001095:Arachidonic Acids; D008041:Linoleic Acids; D010743:Phospholipids; D014280:Triglycerides; D016718:Arachidonic Acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D019787:Linoleic Acid; D000242:Cyclic AMP