Elimination of smooth muscle cells in experimental restenosis: targeting of fibroblast growth factor receptors.
Factors in plasma and platelets do not fully account for the proliferation of smooth muscle cells in vascular injury, implying that additional factors are involved. Recently, we and others have observed that vascular injury regulates basic fibroblast growth factor, suggesting a further role for this pleiotropic factor. We report here that injury of rat arteries leads to an increase in fibroblast growth factor receptors in vascular smooth muscle cells. This up-regulation makes smooth muscle cells susceptible, in vitro and in vivo, to the lethal effects of a conjugate of basic fibroblast growth factor with the ribosome inactivator saporin. Saporin alone has no effect, whereas the conjugate kills proliferating, but not quiescent, smooth muscle cells in vitro. In vivo, one to three doses inhibit neointimal proliferation but have no apparent effect on the uninjured artery. Thus, the up-regulation of fibroblast growth factor receptors in vascular injury suggests new therapeutic possibilities for such refractory conditions as restenosis following balloon angioplasty.
Casscells
W
W
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Lappi
D A
DA
Olwin
B B
BB
Wai
C
C
Siegman
M
M
Speir
E H
EH
Sasse
J
J
Baird
A
A
D000595:Amino Acid Sequence; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000906:Antibodies; D001011:Aorta / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D001157:Arterial Occlusive Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D000922:Immunotoxins; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009699:N-Glycosyl Hydrolases; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D000906:Antibodies; D000922:Immunotoxins; D010455:Peptides; D010940:Plant Proteins; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D016222:Fibroblast Growth Factor 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins