Rapamycin inhibits vascular smooth muscle cell migration

Michael Poon, Steven O. Marx, Richard Gallo, Juan José Badimon, Mark B. Taubman, Andrew R. Marks

Research output: Contribution to journalArticlepeer-review

476 Scopus citations

Abstract

Abnormal vascular smooth muscle cell (SMC) proliferation and migration contribute to the development of restenosis after percutaneous transluminal coronary angioplasty and accelerated arteriopathy after cardiac transplantation. Previously, we reported that the macrolide antibiotic rapamycin, but not the related compound FK506, inhibits both human and rat aortic SMC proliferation in vitro by inhibiting cell cycle-dependent kinases and delaying phosphorylation of retinoblastoma protein (Marx, S.O., T. Jayaraman, L.O. Go, and A.R. Marks. 1995. Circ. Res. 362:801). In the present study the effects of rapamycin on SMC migration were assayed in vitro using a modified Boyden chamber and in vivo using a porcine aortic SMC explant model. Pretreatment with rapamycin (2 ng/ml) for 48 h inhibited PDGF-induced migration (PDGF BB homodimer; 20 ng/ml) in cultured rat and human SMC (n = 10; P < 0.0001), whereas FK506 had no significant effect on migration. Rapamycin administered orally (1 mg/kg per d for 7 d) significantly inhibited porcine aortic SMC migration compared with control (n = 15; P < 0.0001). Thus, in addition to being a potent immunosuppressant and antiproliferative, rapamycin also inhibits SMC migration.

Original languageEnglish
Pages (from-to)2277-2283
Number of pages7
JournalJournal of Clinical Investigation
Volume98
Issue number10
DOIs
StatePublished - 15 Nov 1996
Externally publishedYes

Keywords

  • FK506
  • FKBP12
  • atherosclerosis
  • immunophilin
  • restenosis

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