Glucocorticoid-Related Impairment in the Metabolism of Low Density Lipoprotein by Human Fibroblasts

Summary

The metabolism of radiolabelled ¹²⁵I-low density lipoprotein (LDL) was studied in cultured human dermal fibroblasts to investigate potential mechanisms contributing to the accelerated development of cardiovascular disease in patients treated chronically with corticosteroids. Fibroblasts exposed for 48 hours to pooled lipoprotein-poor (d > 1.25gm/ml) serum from glucocorticoid-treated patients showed an increased capacity to bind LDL (p <.001) compared to cells incubated under identical conditions with pooled serum from controls. In addition, a significantly (p < .001) reduced amount of soluble radioactive material appeared in the media indicating that exposure of fibroblasts to corticosteroid serum also impaired their capacity to degrade LDL. If this tendency of cultured cells to accumulate cholesterol-rich lipoprotein when exposed to constituents of serum from these patients is present in patients receiving long-term treatment with glucocorticoids, it might influence arterial lipid accumulation and accelerate their developing cardiovascular disease.

Key-Words

Glucocorticoids - Fibroblasts - Low Density Lipoprotein - Metabolism - Atherogenesis