Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. Normalization with bezafibrate therapy.

Abstract

The metabolism of hypertriglyceridemic low density lipoprotein (HTG-LDL) was investigated in upregulated cultured human skin fibroblasts. Low density lipoprotein (LDL) was isolated by zonal centrifugation from the plasma of seven HTG subjects, before and 2 wk after the initiation of bezafibrate (BZ) therapy. HTG-LDL is a cholesterol-poor, triglyceride-rich lipoprotein of smaller diameter than BZ-LDL or normal LDL (N-LDL). Binding, cell association, and proteolytic degradation of HTG- LDL were compared with that of BZ-LDL and N-LDL and were found to be significantly lower by a paired t test analysis (P < 0.001). After 6 h preincubation with unlabeled HTG- LDL, the incorporation of [14Clacetate to sterols was signifi- cantly higher than with BZ-LDL or N-LDL (57743.7; 33041.5; 26247, meanSE, picomoles sterols per milligram cell protein per 2 h, respectively; P < 0.001 by paired t test).