VITAMIN-E ATTENUATES INDUCTION OF ELASTASE-LIKE ACTIVITY BY TUMOR-NECROSIS-FACTOR-ALPHA, CHOLESTAN-3-BETA,5-ALPHA,6-BETA-TRIOL AND LINOLEIC-ACID IN CULTURED ENDOTHELIAL-CELLS

Disturbances in arterial wall elastin metabolism appear to be importan t factors in atherosclerosis development. To evaluate this hypothesis, elastase-like activity was determined in cultured endothelial cells a nd their surrounding media after exposure to tumor necrosis factor-alp ha (TNF), cholestan-3beta,5alpha,6beta-triol (Triol) and linoleic acid (18:2). Significant increases in elastase-like activity both in the c ells and in the media were observed when subconfluent endothelial cell s were treated with 12 muM Triol, 500 U TNF/ml, or 90 muM 18:2, for 72 h in the presence of 5% calf serum. Eyen higher activities were measu red when endothelial cells were seeded directly into media enriched wi th 18:2, TNF or Triol and treated for 72 h. Vitamin E supplementation (25 muM) attenuated elastase-like activity in cells and media, indepen dent of treatment. These results suggest that elastase-like enzyme ind uction in endothelial cells may be involved in cellular perturbations induced by certain lipids and cytokines. Vitamin E may provide a prote ctive function by preventing the induction of elastolytic enzymes. Thi s may have implications in elastin metabolism and atherosclerosis.