Low density lipoprotein receptor-related protein mediates apolipoprotein E inhibition of smooth muscle cell migration.
This research was undertaken to identify the cell surface receptor responsible for mediating apolipoprotein E (apoE) inhibition of platelet-derived growth factor (PDGF)-directed smooth muscle cell migration. Initial studies revealed the expression of the low density lipoprotein receptor (LDLR), the LDL receptor-related protein (LRP), the very low density lipoprotein receptor (VLDL), and apoE receptor-2 in mouse aortic smooth muscle cells. Smooth muscle cells isolated from LDLR-null, VLDL-null, and apoE receptor-2-null mice were responsive to apoE inhibition of PDGF-directed smooth muscle cell migration, suggesting that these receptors were not involved. An antisense RNA expression knockdown strategy, utilizing morpholino antisense RNA against LRP, was used to reduce LRP expression in smooth muscle cells to assess the role of this receptor in apoE inhibition of cell migration. Results showed that apoE was unable to inhibit PDGF-directed migration of LRP-deficient smooth muscle cells. The role of LRP in mediating apoE inhibition of PDGF-directed smooth muscle cell migration was confirmed by experiments showing that antibodies against LRP effectively suppressed apoE inhibition of PDGF-directed smooth muscle cell migration. Taken together, these results document that apoE binding to LRP is required for its inhibition of PDGF-directed smooth muscle cell migration.
Swertfeger
Debi K
DK
Center for Lipid and Arteriosclerosis Studies, Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Bu
Guojun
G
Hui
David Y
DY
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D001483:Base Sequence; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001057:Apolipoproteins E; D017931:DNA Primers; D026502:LDL-Receptor Related Proteins