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 whi ch may be mediated by alterations in normal proteoglycan synthesis/met abolism. 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. Ind ependent exposure to 1 mM beta-D-xyloside or 90 mu M 18:2 increased al bumin transfer, i.e., decreased barrier function, when compared with c ontrol cultures. 18:2 and beta-D-xyloside increased albumin transfer a dditively, suggesting that the mechanisms by which 18:2 and beta-D-xyl oside alter the proteoglycan metabolism are different. Compared with t he 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 sulfat e proteoglycan into the culture media. Treatment with beta-D-xyloside caused an increased incorporation of radioactive sulfate into glycosam inoglycans but inhibited proteoglycan synthesis. These results suggest that the fatty acid- and beta-D-xyloside-induced impairment in endoth elial barrier function may involve changes in the synthesis, release a nd physicochemical properties of proteoglycans.