Oxidized lipid-mediated alterations in proteoglycan metabolism in cultured pulmonary endothelial cells.
Compared to cholesterol or linoleic acid (18:2), oxidized lipids such as cholestan-3 beta, 5 alpha, 6 beta-triol (triol) and hydroperoxy linoleic acid (HPODE) markedly impair endothelial barrier function in culture [Hennig and Boissonneault, 1987; Hennig et al. 1986]. Because proteoglycans contribute to vascular permeability properties, the effects of cholesterol and 18:2 and their oxidation products, triol and HPODE, on endothelial proteoglycan metabolism were determined. While cholesterol was without effect, a concentration-dependent decrease in cellular proteoglycans (measured by 35S incorporation) was observed after exposure to triol. Compared to control cultures, cholesterol reduced mRNA levels for the proteoglycans, perlecan and biglycan. Triol had a similar effect on biglycan but not an perlecan mRNA levels. Compared to 18:2, 1,3 and 5 microM HPODE depressed cellular proteoglycans. Perlecan mRNA levels were reduced more by HPODE when compared to 18:2. Biglycan mRNA levels were reduced by 3 microM, but not by 5 microM HPODE. These data demonstrate that oxidized lipids such as triol and HPODE can decrease cellular proteoglycan metabolism in endothelial monolayers and alter mRNA levels of major specific proteoglycans in a concentration-dependent manner. This may have implications in lipid-mediated disruption of endothelial barrier function and atherosclerosis.
Ramasamy
S
S
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506, USA.
Lipke
D W
DW
Boissonneault
G A
GA
Guo
H
H
Hennig
B
B
D000818:Animals; D058578:Biglycan; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002777:Cholestanols / Q000494:pharmacology*; D002784:Cholesterol / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000235:genetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013552:Swine
D058578:Biglycan; D002777:Cholestanols; D002784:Cholesterol; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D019787:Linoleic Acid; D008041:Linoleic Acids; D011509:Proteoglycans; D012333:RNA, Messenger; C000474:cholestane-3,5,6-triol; C075807:8-hydroperoxylinoleic acid; C071927:perlecan