[The cytotoxicity of oxidized lipoproteins]

The peroxidation of low-density lipoproteins (LDL) and their subsequent cytotoxicity is believed to be involved in the atherogenesis. The aim of this work was to determine the possible involvement of lipid peroxides in the cytotoxicity of lipoproteins. We report a new experimental model system constituted by lipoproteins treated by short-UV radiations which result in a major lipid peroxidation without functional alteration of apoproteins. UV radiations induced the following lipid modifications: the content of polyunsaturated fatty acids decreased considerably in all lipid classes; the level of natural antioxidants, i.e. vitamin E and carotene, dropped dramatically; conjugated dienes and thiobarbituric acid reactive substances (TBARS) were notably increased; apoproteins from LDL exhibited little structural modification but no functional alteration. The cytotoxicity was studied in lymphoblastoid cell lines established from lymphocytes derived from normal subjects or from patients with familial hypercholesterolemia. High density lipoproteins (HDL) were shown to inhibit the cytotoxicity induced by low doses of peroxidized LDL; the protective effect of HDL was complete up to the ratio ApoB/ApoA close to 1. In addition, vitamin E and catechin, two well known antioxidants, blocked the cytotoxicity of peroxidized LDL. These results corroborate the possibility of the synergic effect of HDL and antioxidant molecules for the protection of cells against oxidized LDL that are incorporated through the LDL-receptor pathway.