Modification of low density lipoprotein metabolism by growth factors in cultured vascular cells and human skin fibroblasts. Dependence upon duration of exposure.

The influences of specific growth factors upon binding, internalization and degradation of low density lipoproteins (LDL) were investigated in cultured vascular smooth muscle cells and skin fibroblasts. Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) significantly stimulated the binding of LDL to high affinity receptors of smooth muscle cells and fibroblasts. The effects of enhanced binding were reflected in elevated rates in internalization and degradation of LDL. FGF and PDGF elicited a mitogenic response as measured by [3H]thymidine autoradiography, indicating that altered LDL metabolism was associated with entry into the cell cycle. When fibroblasts were exposed to mitogen for periods long enough to commit the cells to the growth cycle, after which growth factor was removed before addition of LDL however, enhanced LDL binding to cycling fibroblasts appeared to be dependent upon the length of the period of exposure to growth factors in the early part of the cell cycle. LDL binding was stimulated in the presence of PDGF or FGF but not after their removal within 8 h of entry into the cell cycle. Exposure to the growth factors for 16 h or longer resulted in stimulation of LDL metabolism whether or not mitogens were present at the cell surface. PDGF and FGF, therefore, appear to exert a direct influence upon LDL receptor expression in addition to that mediated via the cell cycle.