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 postprandial lipemia and atherogenesis. It was of interest to study the influence of dietary fatty acid composition on the oxidizability and subsequent cytotoxicity of chylomicrons on cultured cells. Human chylomicrons were obtained from healthy volunteers 3 h after ingestion of a triglyceride-rich meal containing mainly either polyunsaturated fatty acids (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 chylomicrons enriched with monounsaturated or saturated fatty acids were relatively resistant to oxidation. The cytotoxicity of various types of chylomicrons submitted to oxidation has been tested comparatively on cultured human monocytic U937 cells and endothelial cells. Chylomicrons enriched with saturated and monounsaturated fatty acids were not or only slightly cytototoxic to cultured cells, whereas PUFA-rich chylomicrons (highly susceptible to oxidation) were highly cytotoxic. The influence 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 cholesterol-rich chylomicrons were slightly more oxidizable and more cytotoxic than PUFA-rich (cholesterol-poor) chylomicrons, thus suggesting that the cytotoxicity of PUFA-rich chylomicrons may be due to oxidation derivatives of PUFA (for the major part) and to oxysterols (for a minor part). Furthermore, the cytotoxic effects of oxidized PUFA-rich chylomicrons 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 nonnegligible role in cytotoxic events occurring during atherogenesis. In conclusion, our study demonstrates, for the first time to our knowledge, that1: (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).