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Eicosanoids in sickle cell disease: potential relevance of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid to the pathophysiology of vaso-occlusion.

Abstract
The monohydroxyeicosanoid 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), which is derived from oxygenation of arachidonic acid by 12-lipoxygenase, is one of the major metabolites in platelets. In a recent study, we have showed that this eicosanoid stimulated basal sickle-red-cell-endothelial-cell adhesion. To understand the pathophysiologic significance of 12-HETE, we measured the levels of this eicosanoid in plasma and urine from children with sickle cell disease. We found that as compared with controls, plasma 12-HETE levels are increased in patients with sickle-cell disease in the steady state, and are increased further during vaso-occlusive crises. Urinary 12-HETE levels were also increased during the steady state. We also assessed plasma levels of soluble P-selectin (another potential marker for platelet activation), and found changes in the levels of this marker similar to those seen with plasma 12-HETE. In additional studies, we found that 12-HETE enhanced hypoxia-induced sickle-red-cell-endothelial adherence, and that this effect was mediated by potentiation of agonist-induced upregulation of the expression of the mRNA for vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells. Because 12-HETE appears to enhance both basal and agonist-induced sickle-red-cell adhesion, this metabolite could potentially play a role in the pathogenesis of the vaso-occlusive crisis (VOC) in sickle-cell disease.
AuthorsB N Setty, D Chen, P O'Neal, J B Littrell, M H Grossman, M J Stuart
JournalThe Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 131 Issue 4 Pg. 344-53 (Apr 1998) ISSN: 0022-2143 [Print] United States
PMID9579388 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • P-Selectin
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Topics
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid (blood, physiology, urine)
  • Adolescent
  • Adult
  • Anemia, Sickle Cell (blood, physiopathology, urine)
  • Animals
  • Arterial Occlusive Diseases (blood, physiopathology, urine)
  • Cattle
  • Cell Adhesion
  • Child
  • Child, Preschool
  • Endothelium, Vascular (pathology)
  • Gene Expression Regulation (physiology)
  • Humans
  • Middle Aged
  • P-Selectin (blood)
  • RNA, Messenger (genetics)
  • Vascular Cell Adhesion Molecule-1 (genetics)

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