Studies on Cholesterol Turnover in Hypercholesterolemic Subjects

Abstract

In 4 patients with primary hypercholesterolemia (plasma cholesterol concentration: 354-438 mg/100 ml) several parameters of cholesterol turnover were calculated from the specific activity time curve of plasma cholesterol following an intravenous injection of labelled cholesterol, on the basis of a two-exchangeable pool model. The results were compared with the corresponding values of 16 normocholesterolemic subjects (plasma cholesterol concentration: 164-282 mg/100 ml).

The mean size of the more rapidly exchangeable pool A (which essentially includes cholesterol of plasma, erythrocytes, bile, liver, intestine and some cholesterol of other organs such as spleen, kidney and lung) was significantly increased in the hypercholesterolemic subjects. This increase in the size of pool A was accounted for by the increased size of the plasma cholesterol pool which forms part of pool A. After subtraction of the plasma cholesterol pool from pool A, there was no difference in the mean size of the remaining pool A between the normo- and hypercholesterolemic subjects.

Between the two groups of subjects, there was also no difference in the production rate of cholesterol (PR_A; synthesis plus absorption), the net removal rate of cholesterol from the whole system (r_A) and the net transfer rates of cholesterol between pool A and the more slowly exchangeable pool B (r_AB, r_BA). The size of pool B (which includes exchangeable cholesterol in tissues other than pool A) was not different in the hypercholesterolemics as compared with that of the normals.

The mean fractional turnover rate of cholesterol in pool A (k_AA), the mean fractional transfer rate of cholesterol from pool A to pool B (k_AB) and the mean fractional removal rate of cholesterol of pool A from the system (k_A) were lower in the hypercholesterolemic subjects than in the normals. From the studies reported in this paper, it cannot be decided whether the increased plasma cholesterol pool is responsible for the decreased fractional transfer rates of cholesterol from pool A, or whether the decreased fractional removal rate of cholesterol from pool A is responsible for the isolated increase of the plasma cholesterol pool.

The data of these studies is compatible with the hypothesis, that the defect which is responsible for the high plasma cholesterol concentration in primary hypercholesterolemia concerns mainly if not exclusively the turnover of plasma cholesterol and not cholesterol turnover in other exchangeable pools. The question whether there is an increased influx of cholesterol into the plasma or a decreased efflux from the plasma cannot be decided from these studies.

Key words

Cholesterol Turnover - Two Exchangeable Pool Model - Pool Sizes - Transfer Rates - Hypercholesterolemia