Platelet-derived growth factor stimulates low density lipoprotein receptor activity in cultured human fibroblasts.

Abstract

Human platelets contain a mitogen, the platelet-derived growth factor (PDGF), that stimulates the proliferation of a variety of cell types in culture and that may play a role in atherogenesis. Studies were conducted to explore the effects of PDGF on low density lipoprotein (LDL) receptor activity of cultured human fibroblasts. The PDGF utilized in these studies was partially purified from human platelet-rich plasma by ion exchange chromatography and gel filtration. LDL receptor activity was assessed by both specific binding of 125I-labeled LDL to the fibroblast''s surface at 4.degree. C, and the incorporation of [14C]oleate into cholesteryl esters. Exposure of normal human fibroblasts to increasing amounts of PDGF (0.1-10 .mu.g/ml) for 48 h causes a dose-related increase in 125I-labeled LDL binding to a maximum of .apprx. 300%. In the presence of added LDL, this increase in LDL binding was not seen. Cholesterol esterification was also stimulated following a 48 h exposure to PDGF. Following a conditioning period in LDL- and PDGF-depleted medium, cholesterol esterification was greatly increased during a 48 h exposure to LDL alone; a smaller but significant increase occurred with PDGF alone. PDGF and LDL were required to return the level of esterification to that observed with whole human serum. Fibroblasts from a patient with homozygous familial hypercholesterolemia, which lack the LDL receptor, also showed a significant increase in cholesterol esterification with PDGF alone; LDL had no effect. PDGF can stimulate the LDL receptor activity in cultured human fibroblasts. The effect on other related activities of the LDL receptor system and the mechanism involved remain to be defined.