INCREASED J774 MACROPHAGE CYTOTOXICITY OF LATE POSTPRANDIAL TRIGLYCERIDE-RICH LIPOPROTEINS FROM NORMOLIPIDEMIC YOUNG MEN EXPRESSING AN APOLIPOPROTEIN EPSILON-4 ALLELE

It has been demonstrated that normolipidemic young men with apolipopro tein E4/3 phenotype have a prolonged postprandial clearance of triglyc eride-rich lipoproteins following a high-fat diet. In the present stud y, we isolated fasting and postprandial (3 and 8 h) lipoprotein fracti ons from normolipidemic young men with E3/3 and E4/3 phenotypes and ex amined the in vitro cytotoxicity of these lipoproteins towards J774 ma crophages. 8 h E4/3 very low density lipoprotein (VLDL) were significa ntly more cytotoxic than either 8 h E3/3 VLDL or fasting and 3 h E4/3 VLDL (lactate dehydrogenase (LDH) released: 161 +/- 21, 107 +/- 9, 88 +/- 16 and 101 +/- 12 I.U./l, respectively). Fasting E4/3 intermediate density lipoprotein (IDL) were also significantly more cytotoxic than either fasting E3/3 IDL or 3 h and 8 h E4/3 IDL (LDH released: 105 +/ - 23, 60 +/- 9, 37 +/- 5 and 53 +/- 16 I.U./l, respectively), whereas either fasting or postprandial low density lipoprotein (LDL) and high density lipoprotein (HDL) samples did not show any difference in cytot oxicity between the two groups studied. 8 h E4/3 VLDL samples incubate d with J774 macrophages had a lower esterified cholesterol (40 +/- 3 v ersus 52 +/- 3 mu g), and higher triglyceride (783 +/- 133 versus 418 +/- 64 mu g) and free fatty acid (FFA) (2.0 +/- 0.4 versus 0.9 +/- 0.1 mu g) content than fasting E4/3 VLDL. The increased macrophage cytoto xicity of late postprandial triglyceride-rich lipoproteins seems to be related to the FFA content of E4/3 VLDL. (C) 1997 Elsevier Science Ir eland Ltd.