Skip to main content

Loss of p27Kip1 and induction of Cdk1 in the rat carotid artery following ballon catheter injury. in vivo and in vitro influence of rapamycin

Publication ,  Journal Article
Braun-Dullaeus, RC; Von Der Leyen, HE; Mann, MJ; Zhang, L; Morris, RE; Dzau, VJ
Published in: FASEB Journal
December 1, 1997

Vascular smooth muscle cell proliferation (VSMC) is induced in vitro by serum stimulation or in vivo by balloon catheter injury. We hypothesized that a proliferative response involves changes in the expression of the cyclin-dependent kinase Cdk1 and the Cdk-inhibitor p27Kip1 and that these changes might be prevented by rapamycin (RPM). In vitro, serum stimulation of quiescent VSMCs led to a drop of p27Kip1 and upregulation of Cdk1 as measured by immunoblotting. 3H-thymidine incorporation was increased 38 fold in comparison to quiescent cells (24528±1859 vs. 642±118 cpm/well). RPM (100 nM) did not prevent the p27Kip1 drop but inhibited serum induced Cdk1 expression and 3H-thymidine incorporation (936±94 cpm/well, n=4), indicating a G1 arrest. Competition experiments with FK506 showed that the RPM effect was FK binding protein mediated. In vivo, left carotid injury of rats led to a rapid loss of p27Kip1 (nadir after 48 h, n=5). Cdk1 expression was induced maximally 4 days post injury. RPM pretreatment for 4 days prior to injury (6 mg/kg*d, i.p.), failed to prevent the p27Kip1 drop but again prevented the induction of Cdk1 (n=5) in comparison to vehicle treated animals. RPM, known to stabilize p27Kip1 in lymphocytes, acts differently in VSMC cultures and in vivo in vascular tissue. It attenuates the induction of Cdk1 explaining its ability to inhibit VSMC growth and neointimal proliferation after vascular injury.

Duke Scholars

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

December 1, 1997

Volume

11

Issue

3

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Braun-Dullaeus, R. C., Von Der Leyen, H. E., Mann, M. J., Zhang, L., Morris, R. E., & Dzau, V. J. (1997). Loss of p27Kip1 and induction of Cdk1 in the rat carotid artery following ballon catheter injury. in vivo and in vitro influence of rapamycin. FASEB Journal, 11(3).
Braun-Dullaeus, R. C., H. E. Von Der Leyen, M. J. Mann, L. Zhang, R. E. Morris, and V. J. Dzau. “Loss of p27Kip1 and induction of Cdk1 in the rat carotid artery following ballon catheter injury. in vivo and in vitro influence of rapamycin.” FASEB Journal 11, no. 3 (December 1, 1997).
Braun-Dullaeus RC, Von Der Leyen HE, Mann MJ, Zhang L, Morris RE, Dzau VJ. Loss of p27Kip1 and induction of Cdk1 in the rat carotid artery following ballon catheter injury. in vivo and in vitro influence of rapamycin. FASEB Journal. 1997 Dec 1;11(3).
Braun-Dullaeus RC, Von Der Leyen HE, Mann MJ, Zhang L, Morris RE, Dzau VJ. Loss of p27Kip1 and induction of Cdk1 in the rat carotid artery following ballon catheter injury. in vivo and in vitro influence of rapamycin. FASEB Journal. 1997 Dec 1;11(3).

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

December 1, 1997

Volume

11

Issue

3

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology