Casscells W, Lappi D A, Olwin B B, Wai C, Siegman M, Speir E H, Sasse J, Baird A
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7159-63. doi: 10.1073/pnas.89.15.7159.
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.
血浆和血小板中的因子并不能完全解释血管损伤时平滑肌细胞的增殖，这意味着还有其他因子参与其中。最近，我们和其他人观察到血管损伤会调节碱性成纤维细胞生长因子，提示这种多效性因子可能发挥进一步作用。我们在此报告，大鼠动脉损伤会导致血管平滑肌细胞中纤维母细胞生长因子受体增加。这种上调使得平滑肌细胞在体外和体内对碱性成纤维细胞生长因子与核糖体失活剂皂草素的偶联物的致死作用敏感。单独的皂草素没有作用，而该偶联物在体外能杀死增殖的而非静止的平滑肌细胞。在体内，一到三剂可抑制内膜增生，但对未损伤的动脉没有明显影响。因此，血管损伤时纤维母细胞生长因子受体的上调为诸如球囊血管成形术后再狭窄等难治性病症提示了新的治疗可能性。
