OXIDIZED LDL PROMOTES VASCULAR ENDOTHELIAL-CELL PINOCYTOSIS VIA A PROOXIDATION MECHANISM

Human low density lipoprotein (LDL) is prepared in the presence of ant ioxidants and is oxidized to different levels (measured by thiobarbitu ric acid reactive substance) with copper ion. The effects of unoxidize d LDL and oxidized LDL (ox-LDL) on stress fiber formation, cell. membr ane ruffling, and pinocytosis (measured by [C-14]sucrose uptake) in cu ltured human umbilical cord vein endothelial cells (EC) are compared. We show that at a concentration range of 100 to 200 mu g cholesterol/m l, both unoxidized LDL and ox-LDL promote EC elongation and stress fib er formation, but the effect by the latter is more prominent when comp ared at the same dose range. In addition, ox-LDL also induces EC membr ane ruffling and promotes pinocytosis, These effects are positively co rrelated with the extent of LDL oxidation and depend on the dose of ox -LDL, Ox-LDL-promoted membrane ruffling and pinocytosis are effectivel y blocked by brief preexposure of the cells to antioxidants, In contra st, stress fiber formation is not affected by antioxidant pretreatment . Although unoxidized LDL also promotes [C-14]sucrose uptake, it is le ss potent than ox-LDL and significantly higher concentrations are requ ired to produce a detectable effect. Unlike ox-LDL, unoxidized LDL-enh anced pinocytosis is not accompanied by the appearance of membrane ruf fling; therefore, they may act via different mechanisms. Elevated pino cytosis may increase transcytotic activity of the endothelium, leading to an increased influx of plasma components such as LDL into the sube ndothelial space.-Chow, S.-E., Lee, R.-S., Shih, S. H., Chen, J.-K. Ox idized LDL promotes vascular endothelial cell pinocytosis via a prooxi dation mechanism.