Low density lipoprotein metabolism by cultured skin fibroblasts from atherosclerotic patients.

The aim of this study was to determine whether an abnormality in low density lipoprotein (LDL) metabolism could be demonstrated in fibroblasts cultured from normolipidaemic subjects with atherosclerosis. Seventeen male subjects aged 30-55 years with normal plasma lipid concentrations were divided into 2 groups on the basis of the presence or absence of proven coronary artery and/or peripheral vascular disease. LDL metabolism was assessed in cultured fibroblasts obtained from each of these subjects. After 6 h incubation with 125I-labelled LDL, it was found that binding, uptake and degradation of the lipoprotein were all significantly higher in cells from the atherosclerotic group of subjects than the controls. Variations in cellular LDL metabolism were also correlated with 4 risk factors for cardiovascular disease. Plasma LDL concentration in the atherosclerotic subjects was found to be inversely related to LDL binding and degradation. Subject age was inversely related to LDL degradation in both groups of subjects. No association was demonstrated in either group of subjects between LDL metabolism and glucose intolerance, or between LDL metabolism and cigarette smoking. It is concluded from these results that cellular LDL binding may constitute a factor in determining the rate of atheroma formation, which is independent of other cardiovascular risk factors.