13-Hydroxyoctadecadienoic acid (13-HODE) metabolism and endothelial cell adhesion molecule expression: effect on platelet vessel wall adhesion.
Endothelial cells synthesize two important fatty acid metabolites, PGI2, which is synthesized from arachidonic acid via the cyclooxygenase pathway, and 13-HODE, which is synthesized from linoleic acid via the lipoxygenase pathway. PGI2 is synthesized following cell activation or injury while 13-HODE is synthesized in the unstimulated cell. While the role of PGI2 in platelet vessel wall interactions has been studied extensively, the role of 13-HODE in platelet vessel wall interactions is just now being understood. The present evidence suggests that 13-HODE is continuously synthesized in "resting" vessel wall cells and is in close juxtaposition with the ubiquous integrin adhesion molecule, the vitronectin receptor. The observation that the endothelial cell is not adhesive when 13-HODE and the vitronectin receptor are in close association and becomes adhesive when these two moieties dissociate and the vitronectin receptor relocates on the surface of the cell, provides further evidence that 13-HODE may induce conformational changes in the vitronectin receptor to reduce its ability to recognize its adhesive ligands. The additional observations that 13-HODE levels in both human and animal vessel walls are inversely related with vessel wall adhesivity, and that this adhesivity can be altered by altering 13-HODE synthesis, provides evidence that 13-HODE down-regulates the thrombogenecity of the injured vessel wall surface.
Buchanan
M R
MR
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Bertomeu
M C
MC
Brister
S J
SJ
Haas
T A
TA
D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D008041:Linoleic Acids / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000502:physiology*; D016024:Receptors, Cytoadhesin / Q000502:physiology*; D019030:Receptors, Vitronectin; D013927:Thrombosis / Q000097:blood*
D008041:Linoleic Acids; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; C024348:13-hydroxy-9,11-octadecadienoic acid