Effect of copper deficiency on the composition of three high-density lipoprotein subclasses as separated by heparin-affinity chromatography

Abstract

Copper deficiency in rats produces a hypercholesterolemia with a marked increase in HDL fraction. This study investigated changes in the plasma distribution and composition of HDL subclasses as affected by copper deficiency. Plasma HDL were separated into the following three subclasses by heparin-affinity chromatography: HDL containing no apo E but high in apo A-I (HDL-E 0); HDL with an intermediate level of apo E (HDL-E 1); and HDL highly enriched in apo E but low in apo A-I (HDL-E 2). The compositional analysis showed that the hypercholesterolemia observed in copper-deficient rats was due specifically to an increase in plasma cholesterol carried by HDL-E 0. Copper deficiency did not alter the percent distribution of apo A-I in HDL-E 0, but lowered the apo A-I content in HDL-E 1 and HDL-E 2, with an increase in apo E in these subclasses. The total plasma concentration of apo A-I was, however, significantly elevated in Cu-deficient rats, which was attributable to an increase in the total number of circulating HDL particles. No difference was noted between Cu-deficient and control groups in the distribution of free cholesterol or the ratio of free cholesterol to esterified cholesterol in any of the HDL subclasses. The present results and earlier observations suggest that copper deficiency may produce a defect in the plasma clearance or tissue uptake of the HDL subclass high in apo A-I but devoid of apo E (HDL-E 0), which may be mediated by the specific apo A-I receptor or non-endocytotic transfer of HDL-E 0 cholesterol to the liver. Such metabolic defects may partly explain the simultaneous increases in both plasma HDL cholesterol and apo A-I and altered cholesterol homeostasis observed in copper deficiency.