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 linol eic acid (HPODE) markedly impair endothelial barrier function in cultu re [Hennig and Boissonneault, 1987; Hennig et al. 1986]. Because prote oglycans contribute to vascular permeability properties, the effects o f cholesterol and 18:2 and their oxidation products, triol and HPODE, on endothelial proteoglycan metabolism were determined. While choleste rol was without effect, a concentration-dependent decrease in cellular proteoglycans (measured by S-35 incorporation) was observed after exp osure to triol. Compared to control cultures, cholesterol reduced mRNA levels for the proteoglycans, perlecan and biglycan. Triol had a simi lar effect on biglycan but not on perlecan mRNA levels. Compared to 18 :2, 1, 3 and 5 mu M HPODE depressed cellular proteoglycans. Perlecan m RNA levels were reduced more by HPODE when compared to 18:2. Biglycan mRNA levels were reduced by 3 mu M, but nor by 5 mu M HPODE. These dat a demonstrate that oxidized lipids such as triol and HPODE can decreas e cellular proteoglycan metabolism in endothelial monolayers and alter mRNA levels of major specific proteoglycans in a concentration-depend ent manner. This may have implications in lipid-mediated disruption of endothelial barrier function and atherosclerosis.