Rapamycin inhibits vascular smooth muscle cell migration.

We reported that the macrolide antibiotic rapamycin, but not the related compound FK506, inhibits both human and rat aortic smooth muscle cell proliferation in vitro by inhibiting cell cycle–dependent kinases and delaying phosphorylation of retinoblastoma protein (Marx, S.O., T

M Poon; S O Marx; R Gallo; J J Badimon; M B Taubman; A R Marks


Scholarcy highlights

  • Abnormal vascular smooth muscle cell1 proliferation and migration play major roles in the formation of atherosclerotic plaques, in the development of restenosis after percutaneous transluminal angioplasty and in accelerated arteriopathy after cardiac transplantation
  • In rat aortic SMC, the inhibition of rapamycin of both proliferation and migration is mediated through a novel form of FKBP12 which contains three amino acid substitutions compared with the human FKBP12, including a serine substitution for a highly conserved proline at residue 10
  • This study demonstrates that rapamycin inhibits rat, porcine, and human SMC migration
  • We have previously demonstrated that rapamycin has antiproliferative effects on rat and human aortic SMC mediated by binding to FKBP12 and inhibiting cell cycle kinases and delaying phosphorylation of retinoblastoma protein
  • Whether the antimigratory actions of rapamycin-FKBP12 in SMC involve any of these signaling molecules remains unproven
  • The present study suggests that rapamycin can be used as a “molecular probe” to dissect signaling pathways regulating SMC migration in much the same way as the drug is being used to gain insight into mechanisms controlling cell growth
  • The morphology of smooth muscle cell from treated and untreated cultures and tissue sections was indistinguishable, suggesting that rapamycin does not appear to have an effect on the cytoskeletal components that have been associated with migration

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