Changes in very low density lipoproteins with cholesterol loading in man

We have studied the effects of cholesterol loading in man, seeking changes in VLDL that may define a population of particles that resemble the atherogenic β-VLDL in experimental animals. Comparisons were made in 6 men during two diets, containing either 200 mg or 1700 mg cholesterol daily. Although the total plasma cholesterol did not rise significantly over 4 wk of cholesterol loading (mean ± SD 178 ± 41 to 194 ± 48 mg/dl), distinct changes in lipoprotein composition occurred; (1) HDL cholesterol rose significantly (34 ± 4 to 41 ± 5) and plasma apoprotein Al rose from 118 ± 10 to 129 ± 9 mg/dl, (2) Within VLDL, the proportion of apoproteins E:C rose from 0.18 to 0.32 (p < 0.005), though the apoprotein E concentration did not change, (3) Within VLDL, the ratio of cholesteryl esters:triglyceride rose, (4) Within VLDL (Sf 20–400) a population of particles that bound to heparin on heparin-sepharose columns increased threefold; since these particles were richer in apoprotein E and in cholesteryl ester than were VLDL not bound to heparin, we conclude that cholesterol loading leads to an increase in smaller VLDL particles, possibly partly catabolized VLDL or independently secreted IDL, that resemble findings in cholesterol fed animals, and (5) Transport kinetics of apoprotein B in VLDL studied in four subjects did not show a rise in production but this does not rule out increased secretion of a cholesteryl ester, apoprotein E enriched subpopulation of VLDL.