Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/6975
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Type: Journal article
Title: Inhibitory effects of arachidonic acid (20:4, n-6) and its monohydroxy-and hydrodrymetabolites on procoagulant activity in endothelial cells
Author: Bates, E.
Ferrante, A.
Smithers, L.
Poulos, A.
Rathjen, D.
Robinson, B.
Citation: Atherosclerosis, 1995; 116(1):125-133
Publisher: Elsevier Scientific Publ. Co.
Issue Date: 1995
ISSN: 0021-9150
1879-1484
Statement of
Responsibility: 
Bates, Edna J. ; Ferrante, Antonio ; Poulos, Alf ; Smithers, Lisa ; Rathjen, Deborah A. ; Robinson, Brenton S.
Abstract: The procoagulant response of endothelium to pathophysiological agents such as tumour necrosis factor alpha (TNF alpha) and phorbol myristate acetate (PMA) alters the expression of proteins such as tissue factor. The modulation of such procoagulant activity (PCA) by the polyunsaturated fatty acid arachidonic acid (20:4,n-6) and its 15-hydroperoxy (15-HPETE) and 15-hydroxy (15-HETE) metabolites was examined since this may have important implications in cardiovascular disease and atherosclerosis. Treatment of human umbilical vein endothelial cells (HUVEC) for 30 min with 20:4, 15-HPETE or 15-HETE before induction of PCA with TNF alpha (100 U) or PMA (10(-7) M) caused a significant inhibition of PCA. This inhibition was seen at 2-5 microM fatty acids. Dose response curves with TNF alpha indicated that the inhibition was greatest at higher concentrations of TNF alpha (> or = 250U TNF alpha/ml). The mode of administration of the fatty acid was not critical as fatty acids presented as DPC-fatty acid micelles or solubilised in ethanol gave similar inhibitions of PCA. 20:4, 15-HPETE or 15-HETE did not alter the binding of I125-labelled TNF alpha to its surface receptors on HUVEC, suggesting that the effect of these fatty acids was not mediated by events at the cell surface receptor level. In support of this, these fatty acids were found to inhibit PCA induced by PMA which bypasses cell surface receptors to activate protein kinase C directly.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords: Endothelium, Vascular; Umbilical Veins; Cells, Cultured; Humans; Tetradecanoylphorbol Acetate; Lipid Peroxides; Arachidonic Acid; Hydroxyeicosatetraenoic Acids; Leukotrienes; Tumor Necrosis Factor-alpha; Blood Coagulation Factors; Thromboplastin; Recombinant Proteins; Gene Expression Regulation
RMID: 0030005755
DOI: 10.1016/0021-9150(95)05538-8
Appears in Collections:Paediatrics publications

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