IMPACT OF LDL CAROTENOID AND ALPHA-TOCOPHEROL CONTENT ON LDL OXIDATION BY ENDOTHELIAL-CELLS IN CULTURE

Carotenoids and alpha-tocopherol are dietary, lipophilic antioxidants that may protect plasma lipoproteins from oxidation, a process believe d to contribute to atherogenesis, Previous work demonstrated that afte r the Cu(II)initiated oxidation of human low density lipoprotein (LDL) in vitro, carotenoids and alpha-tocopherol were destroyed before sign ificant lipid peroxidation took place, and that alpha-tocopherol was d estroyed at a much faster rate than were the carotenoids, Additionally , in vitro enrichment of LDL with beta-carotene, but not with lutein o r lycopene, inhibited LDL oxidation, In the present studies the impact of LDL carotenoid and alpha-tocopherol content on LDL oxidation by hu man endothelial cells (EaHy-1) in culture was assessed. LDL isolated f rom 11 individual donors was incubated at 0.25 mg protein/mL with EaHy -1 cells in Ham's F-IO medium for up to 48 h., Formation of lipid hydr operoxides was assessed by chemical analysis and the contents of lutei n, beta-cryptoxanthin, lycopene, beta-carotene and alpha-tocopherol we re determined by high performance liquid chromatography, The extent of Lipid peroxidation correlated with the endogenous alpha-tocopherol co ntent of the LDL but not with its content of carotenoids, As in the Cu (II)-initiated system, carotenoids and alpha-tocopherol were destroyed before significant peroxidation took place, but, in the cell-mediated system, alpha-tocopherol and the carotenoids were destroyed at compar able rates. Also, like the Cu(II)-initiated oxidation, enrichment of t he LDL with beta-carotene protected it from oxidation by the endotheli al cells, However, enrichment with either lutein or lycopene actually enhanced the cell mediated oxidation of the LDL.ir Thus, the specific content of carotenoids in low density lipoprotein (LDL) clearly modula tes its susceptibility to oxidation, but individual carotenoids may ei ther inhibit or promote LDL oxidation.