TRANSIENT TRIGLYCERIDEMIA IN HEALTHY NORMOLIPIDEMIC MEN INCREASES CELLULAR PROCESSING OF LARGE VERY-LOW-DENSITY LIPOPROTEINS BY FIBROBLASTSIN-VITRO

Exaggerated and prolonged postprandial triglyceridemia is a characteri stic of patients with precocious coronary heart disease. Although larg e very low density lipoprotein (VLDL) particles accumulate during alim entary lipemia, the biological properties of the postprandial VLDL rem ain unknown. In the present study, an intravenous infusion of a chylom icron-like emulsion was given to healthy normolipidemic men to examine the effects of transient triglyceridemia in vivo on compositional and cell biological characteristics of VLDL. The postinfusion large(Svedb erg flotation rate (S-f) (60-400) VLDL was found to have increased cap acity to inhibit low density lipoprotein (LDL) binding to the LDL-rece ptor and a greater ability to suppress the 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase activity of cultured fibroblasts compared to V LDL, isolated from fasting plasma. These alterations in cellular inter actions were accompanied by increases in the number of apolipoprotein (ape) E, CI, and C-III molecules per large VLDL particle and loss of a poC-II, compositional changes similar to those observed after an oral fat load. The increase in number of apoE molecules per large VLDL part icle correlated positively and significantly with the increase in the capacity of large VLDL to inhibit LDL binding to the LDL receptor (r = 0.76, P = 0.01, n = 10). In contrast, the composition of the small (S -f 20-60) VLDL particles did not change significantly, nor was the LDL receptor-mediated processing of these particles altered consistently. These observations indicate that large VLDL particles that accumulate during alimentary lipemia undergo compositional changes that render t hem more prone to cellular binding and uptake.