Proteoglycans and endothelial barrier function: effect of linoleic acid exposure to porcine pulmonary artery endothelial cells.
Certain fatty acids induce changes in endothelial barrier function which may be mediated by alterations in normal proteoglycan synthesis/metabolism. To test this hypothesis, pulmonary artery derived endothelial cells were treated with media supplemented with linoleic acid (18:2), and/or a known proteoglycan synthesis inhibitor, beta-D-xyloside. Independent exposure to 1 mM beta-D-xyloside or 90 microM 18:2 increased albumin transfer, i.e., decreased barrier function, when compared with control cultures. 18:2 and beta-D-xyloside increased albumin transfer additively, suggesting that the mechanisms by which 18:2 and beta-D-xyloside alter the proteoglycan metabolism are different. Compared with the control group, treatment with 18:2 inhibited proteoglycan synthesis, decreased anionic properties of heparan sulfate proteoglycans in the cell monolayers and caused the release of a unique chondroitin sulfate proteoglycan into the culture media. Treatment with beta-D-xyloside caused an increased incorporation of radioactive sulfate into glycosaminoglycans but inhibited proteoglycan synthesis. These results suggest that the fatty acid- and beta-D-xyloside-induced impairment in endothelial barrier function may involve changes in the synthesis, release and physicochemical properties of proteoglycans.
Ramasamy
S
S
Department of Nutrition, College of Pharmacy, University of Kentucky, Lexington 40506.
Boissonneault
G A
GA
Lipke
D W
DW
Hennig
B
B
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D006027:Glycosides / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism*; D013552:Swine
D000418:Albumins; D006027:Glycosides; D008041:Linoleic Acids; D011509:Proteoglycans; C010807:xylosides; D019787:Linoleic Acid; D004121:Dimethyl Sulfoxide