Role of Apolipoprotein E-containing Lipoproteins

Received for publication 16 November 1981 and in revised form 18 August 1982. human fibroblasts. The binding activity of plasma from patients (per milligram of protein) was about half that of plasma from normal volunteers. All binding activity in the patients' plasma was found to reside in the HDL fraction. The binding activity of the patients' HDL (on a total protein basis) was intermediate between that of normal HDL and normal LDL. However, the large differences in binding between patients' HDL and normal HDL entirely disappeared when data were expressed in terms of the apoE content of these lipoproteins. This suggested that the binding activity was restricted to that subfraction of HDL particles that contain apoE. These apoE-rich HDL particles had calculated binding potencies per milligram of protein 10-25 times that of normal LDL. Direct binding studies using '25I-apoE-rich HDL2 and 125IapoE-poor HDL2, confirmed the suggestion that binding is restricted to the subfraction of HDL particles containing apoE. The apoE-rich HDL2 were found to be very potent inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity in cultured fibroblasts, providing direct evidence of the ability of these lipoproteins to regulate cholesterol metabolism. On the basis of binding potencies of apoE-rich HDL, apoE concentrations, and the composition of apoE-rich HDL, it could be calculated that apoE-rich HDL in abetalipoproteinemia have a capacity to deliver cholesterol to tissues via the LDL receptor pathway equivalent to an LDL concentration of 50-150 mg/dl of cholesterol. Thus, these apoE-rich lipoproteins are capable of producing the suppression of cholesterol synthesis and LDL receptor activity previously observed in abetalipoproteinemia.