OXIDIZABILITY AND SUBSEQUENT CYTOTOXICITY OF CHYLOMICRONS TO MONOCYTIC U937 AND ENDOTHELIAL-CELLS ARE DEPENDENT ON DIETARY FATTY-ACID COMPOSITION

Oxidized chylomicrons may be a metabolic factor involved in the injury of the arterial wall and may constitute a potential link between post prandial lipemia and atherogenesis. It was of interest to study the in fluence of dietary fatty acid composition on the oxidizability and sub sequent cytotoxicity of chylomicrons on cultured cells. Human chylomic rons were obtained from healthy volunteers 3 h after ingestion of a tr iglyceride-rich meal containing mainly either polyunsaturated fatty ac ids (soya oil) or monounsaturated fatty acids (olive oil) or saturated fatty acids (partly hydrogenated palm oil). Polyunsatured fatty acid (PUFA)-rich chylomicrons exhibited a high oxidizability, whereas chylo microns enriched with monounsaturated or saturated fatty acids were re latively resistant to oxidation. The cytotoxicity of various types of chylomicrons submitted to oxidation has been tested comparatively on c ultured human monocytic U937 cells and endothelial cells. Chylomicrons enriched with saturated and monounsaturated fatty acids were not or o nly slightly cytototoxic to cultured cells, whereas PUFA-rich chylomic rons (highly susceptible to oxidation) were highly cytotoxic. The infl uence of cholesterol on the oxidizability and subsequent cytotoxicity of PUFA-rich chylomicrons has been investigated by using comparatively a soya diet supplemented or not with cholesterol. PUFA-rich cholester ol-rich chylomicrons were slightly more oxidizable and more cytotoxic than PUFA-rich (cholesterol-poor) chylomicrons, thus suggesting that t he cytotoxicity of PUFA-rich chylomicrons may be due to oxidation deri vatives of PUFA (for the major part) and to oxysterols (for a minor pa rt). Furthermore, the cytotoxic effects of oxidized PUFA-rich chylomic rons and of mildly oxidized LDL were in similar range (even higher for PUFA-rich chylomicrons when expressed per lipoprotein particle), thus suggesting that oxidized PUFA-rich chylomicrons may play a nonnegligi ble role in cytotoxic events occurring during atherogenesis. In conclu sion, our study demonstrates, for the first time to our knowledge, tha t(1): (nonlipolyzed) chylomicrons can be cytotoxic to cultured cells;2 the cytotoxicity of (nonlipolyzed) chylomicrons is relative to their oxidation state;(3) the oxidizability (and subsequent cytotoxicity) of chylomicrons is dependent on their PUFA content (depending itself on dietary fatty acid composition).