The magnitude of metabolically induced changes in the density of human low-density lipoproteins

Radiolabelled low-density lipoproteins (LDL), obtained from a patient with heterozygous, familial hypercholesterolaemia and from a normal subject, were injected into the patient and two normal subjects. Two approaches were made to evaluate the kinetics of metabolism of these LDL: (1) by serial measurements of radioactivity in serum, urine and the whole body; (2) by observing the density of the labelled LDL from serum using density-gradient ultracentrifugation. No significant change was seen in the model density of the LDL in either the patient or the normal subjects, but there were changes in the skewness of the radioactivity peaks. This contrasts with previously published findings in the guinea pig, in which LDL radioactivity gradually accumulated in the densest particles. The guinea pig findings suggested that lipoproteins in the LDL region are structurally modified during their intravascular circulation. The present study indicates that modification leading to changes in density does not occur to any significant degree in the human, whose LDL represent the end product of intravascular metabolism of apolipoprotein B-containing lipoproteins.