Rapamycin inhibits vascular smooth muscle cell migration

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

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.

References

    1. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3669-72
    1. Physiol Rev. 1996 Jul;76(3):631-49
    1. Circ Res. 1985 Jan;56(1):139-45
    1. Transplant Proc. 1987 Aug;19(4 Suppl 5):19-25
    1. Nature. 1990 Aug 16;346(6285):671-4
    1. Science. 1990 Oct 26;250(4980):556-9
    1. J Am Coll Cardiol. 1991 May;17(6 Suppl B):77B-88B
    1. Science. 1991 May 10;252(5007):836-9
    1. Science. 1991 Aug 23;253(5022):905-9
    1. Science. 1991 Sep 6;253(5024):1129-32
    1. Gene. 1991 Dec 30;109(2):255-8
    1. J Clin Invest. 1992 Feb;89(2):507-11
    1. J Cell Sci. 1991 Nov;100 ( Pt 3):491-9
    1. Science. 1992 Apr 10;256(5054):245-7
    1. J Biol Chem. 1992 May 15;267(14):9474-7
    1. Nature. 1992 Jul 2;358(6381):70-3
    1. Science. 1992 Aug 14;257(5072):973-7
    1. Circulation. 1992 Sep;86(3):723-9
    1. J Mol Biol. 1993 Jan 5;229(1):105-24
    1. J Clin Invest. 1993 Feb;91(2):547-52
    1. Nature. 1993 Apr 29;362(6423):801-9
    1. Transplantation. 1993 Jun;55(6):1409-18
    1. Gene. 1993 Dec 8;134(2):271-5
    1. Biochem Biophys Res Commun. 1994 Jan 28;198(2):701-6
    1. Nature. 1994 Feb 3;367(6462):474-6
    1. J Clin Invest. 1994 Mar;93(3):1266-74
    1. Cell. 1994 May 20;77(4):513-23
    1. Nature. 1994 Jun 30;369(6483):756-8
    1. Circ Res. 1994 Jul;75(1):41-54
    1. Cell. 1994 Jul 15;78(1):35-43
    1. Science. 1994 Jul 29;265(5172):674-6
    1. J Biol Chem. 1994 Aug 19;269(33):21094-102
    1. Nature. 1994 Dec 8;372(6506):570-3
    1. EMBO J. 1994 Dec 15;13(24):5944-57
    1. Circulation. 1995 Feb 15;91(4):1107-15
    1. Circ Res. 1995 Mar;76(3):412-7
    1. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1784-8
    1. Artery. 1981;9(4):316-27

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다