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Elimination of smooth muscle cells in ex ... roblast growth factor receptors
Elimination of smooth muscle cells in experimental restenosis: targeting of fibroblast growth factor receptors.
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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, Lappi DA, Olwin BB, Wai C, Siegman M, Speir EH, Sasse J, Baird A
Proceedings of the National Academy of Sciences of the United States of America
1992-08-01 00:00
89
15
7159-63
Amino Acid Sequence,Angioplasty, Balloon,Animals,Antibodies,Aorta,Arterial Occlusive Diseases,Cell Division,Cells, Cultured,DNA Replication,Fibroblast Growth Factor 2,Immunohistochemistry,Immunotoxins,Male,Molecular Sequence Data,Muscle, Smooth, Vascular,N-Glycosyl Hydrolases,Peptides,Plant Proteins,Rats,Rats, Inbred Strains,Receptors, Cell Surface,Receptors, Fibroblast Growth Factor,Recombinant Proteins,Antibodies,Immunotoxins,Peptides,Plant Proteins,Receptors, Cell Surface,Receptors, Fibroblast Growth Factor,Recombinant Proteins,Fibroblast Growth Factor 2,N-Glycosyl Hydrolases,RIP protein, Saponaria officinalis
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037
Proc. Natl. Acad. Sci. U.S.A.
NIDDK DK-18811
0027-8424
865
True
1323129
