Antibodies against a putative heparin receptor slow cell proliferation and decrease MAPK activation in vascular smooth muscle cells.
Heparin has long been known to slow the growth of vascular smooth muscle cells. However, the mechanism(s) by which heparin acts has yet to be resolved. The identification of a putative heparin receptor in endothelial cells with antibodies that blocked heparin binding to the cells provided the means to further examine the possible involvement of a heparin receptor in smooth muscle cell responses to heparin. Immunoprecipitation of a smooth muscle cell protein with the anti-heparin receptor antibodies provided evidence that the protein was present in smooth muscle cells. Experiments with the anti-heparin receptor antibodies indicate that the antibodies can mimic heparin in decreasing PDGF induced thymidine and BrdU incorporation. The anti-heparin receptor antibodies were also found to decrease MAPK activity levels after activation similarly to heparin. These results support the identification of a heparin receptor and its role in heparin effects on vascular smooth muscle cell growth.
Savage
J M
JM
Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
Gilotti
A C
AC
Granzow
C A
CA
Molina
F
F
Lowe-Krentz
L J
LJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001011:Aorta; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013552:Swine; D013936:Thymidine / Q000378:metabolism
D000906:Antibodies; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; C037680:heparin receptor; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; D001973:Bromodeoxyuridine; D013936:Thymidine