APOLIPOPROTEIN-E INHIBITS PLATELET-DERIVED GROWTH FACTOR-INDUCED VASCULAR SMOOTH-MUSCLE CELL-MIGRATION AND PROLIFERATION BY SUPPRESSING SIGNAL-TRANSDUCTION AND PREVENTING CELL ENTRY TO G1 PHASE

The anti-atherogenic effects of apolipoprotein (apo) E have been attri buted to its ability to reduce plasma cholesterol level and to limit f oam cell formation. The purpose of this study was to ascertain if apoE also may have cytostatic functions that could attenuate vascular occl usive diseases. Purified apoE inhibited smooth muscle cell migration d irected to platelet-derived growth factor (PDGF) or oxidized LDL (oxLD L) (p < 0.0001). The purified apoE also suppressed PDGF- and oxLDL-ind uced smooth muscle cell proliferation (p < 0.001). These apoE inhibito ry effects were not because of suppression of PDGF binding to its rece ptors on the smooth muscle cells, but was correlated with a significan t reduction in agonist-stimulated mitogen-activated protein kinase act ivity (p < 0.01), ApoE also inhibited PDGF-induced cyclin DI mRNA expr ession, suggesting that the apoE effect was mediated by growth arrest at the G(0) to G(1) phase. Taken together, these results suggest that apoE has cytostatic functions in the vessel wall and may protect again st vascular diseases through inhibition of cell signaling events assoc iated with growth factor-induced smooth muscle cell migration and prol iferation.