Significance of low density lipoprotein production in the regulation of plasma cholesterol level in man

To determine whether production or catabolism of low density lipoprotein (LDL) is the major factor controlling LDL concentrations in subjects with plasma cholesterol levels from low-normal to mildly elevated, measurements of apoprotein of LDL (apoLDL) turnover were performed in 16 patients with various plasma cholesterol concentration. Cholesterol balance studies were done simultaneously in 13 of these patients. Plasma concentrations of apoLDL and LDL-cholesterol were positively correlated with synthetic rates of apoLDL (r = 0.74, P <0.001; r = 0.50, P <0.05, respectively). No correlation was noted between the fractional catabolic rate for apoLDL and apoLDL levels (or LDL-cholesterol). For further analysis, the patients were divided into three groups with stepwise increases in apoLDL concentrations. When apoLDL levels rose significantly, from 83 ± 5 SEM to 122 ± 2 to 149 ±5 mg/dl, synthetic rates for apoLDL also increased significantly from 11.6 ± 1.2 to 17.0 ± 0.9 to 23.8 ± 1.8 mg/d/kg ideal weight. In contrast, the fractional catabolic rates of apoLDL was not different among the three groups(0.32 ± 0.03 vs. 0.29 ± 0.02 vs. 0.33 ± 0.03/d). No relation was noted between synthesis of total body cholesterol (or bile acids) and concentrations, production rates, or removal of apoLDL. Thus, concentrations of apoLDL and LDL-cholesterol in these subjects with plasma cholesterol levels from low-normal to mildly elevated were regulated mainly by synthetic rates of apoLDL and not by LDL catabolism.