INFLUENCE OF LIPOPROTEIN LIPIDS, DIETARY-FAT AND SMOKING ON MACROPHAGE DEGRADATION OF NATIVE AND OXIDIZED LOW-DENSITY-LIPOPROTEIN

Relatively little is known about the biological mechanisms by which li poproteins promote atherogenesis. It has, however, been shown that str uctural modification of low density lipoprotein (LDL), such as by oxid ation, results in their uptake and degradation by intimal macrophages and consequently leads to formation of lipid-rich atherosclerotic lesi ons. The aim of the present investigation was to study the influence o f dietary intake of fat, lipoprotein lipid composition, smoking and ge nder on macrophage degradation of LDL before and after oxidation. The study group consisted of 48 males and 56 females with hyperlipidemia t aking part in the open prerandomization phase of the Probucol Quantita tive Regression Swedish Trial (PQRST). Analysis including lipoprotein determinations, dietary and smoking habit interviews, LDL degradation by macrophages, LDL receptor binding and LDL thiobarbituric acid react ive substance (TBARS) levels before and after copper ion-induced oxida tion was done during the prerandomization phase of the study. Increase d plasma and very low density lipoprotein (VLDL) triglyceride levels w ere associated with an increased macrophage degradation of native LDL, whereas no such association was found after oxidation of LDL. The die tary intake of polyunsaturated fatty acids (PUFA) was also inversely r elated to the degradation of native LDL by macrophages, but increased the rate at which oxidized LDL was degraded. Smoking and gender did no t influence the rate of macrophage degradation of native or oxidized L DL. It is concluded that hypertriglyceridemia is associated with an in creased macrophage degradation of LDL. This may represent a mechanism by which hypertriglyceridemia promotes atherosclerosis.