VITAMIN-E PROTECTS HUMAN AORTIC ENDOTHELIAL-CELLS FROM CYTOTOXIC INJURY-INDUCED BY OXIDIZED LDL IN-VITRO

Human aortic endothelial cells (HAEC) were used to investigate the pro tective role of vitamin E (alpha-tocopherol) against oxLDL in vitro. H AEC exposed to oxLDL (200 mg LDL protein/mL) significantly decreased c ell viability by 36%. HAEC presupplemented with 14, 28, and 53 mu M al pha-tocopherol in the media dose-dependently increased cell resistance to cytotoxic injury from oxLDL (200 mu g protein/mL) as reflected by the number of cells remaining attached to the flask: 3.3 x 10(5), 3.8 x 10(5), 4.9 x 10(5), and 5.2 x 10(5), respectively, versus 5.1 x 10(5 ) in control cultures. Prostacyclin (PGI(2)) produced by HAEC increase d after 12-hr incubation with oxLDL, correlating positively with cell damage and negatively with alpha-tocopherol concentration in the cells . Under the same conditions after a 22-hr incubation, a significant de crease in PGI(2) production was observed only in HAEC pretreated with a high alpha-tocopherol concentration [unsupplemented HAEC: 839 +/- 29 6 pg/mL versus alpha-tocopherol supplemented (53 mu M): 241 +/- 79 pg/ mg]. Interleukin-1 beta production was not detected in HAEC under cont rol conditions or after exposure to oxLDL. HAEC supplemented with alph a-tocopherol but not exposed to oxLDL maintained significantly higher alpha-tocopherol concentrations compared with those exposed to oxLDL. Under phase contrast microscopy, HAEC showed a pronounced elongation o f their normal cobblestone morphology after oxLDL exposure; this chang e was reduced by alpha-tocopherol pretreatment. Thus, supplementation with alpha-tocopherol protected HAEC by reducing the cytotoxic effect of oxLDL, modulating PGI(2) production without having any effect on IL -1 beta. (C) Elsevier Science Inc. 1998.