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A more recent version of this article appeared on October 1, 2007

Published online before print September 6, 2007
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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.061258

Accepted for publication June 26, 2007.

Article

Suppression of Activation of Signal Transducer and Activator of Transcription-5B Signaling in the Vessel Wall Reduces Balloon Injury-Induced Neointima Formation

Venkatesh Kundumani-Sridharan*, Dong Wang*, Manjula Karpurapu*, Zhimin Liu*, Chunxiang Zhang{dagger}, Nagadhara Dronadula*, and Gadiparthi N. Rao*@

From the Departments of Physiology* and Surgery,{dagger} University of Tennessee Health Science Center, Memphis, Tennessee

@ To whom correspondence should be addressed. E-mail: grao{at}physio1.utmem.edu.


  Abstract

Previously, we have demonstrated that STAT-5B plays a role in thrombin-induced vascular smooth muscle cell (VSMC) growth and motility. To learn more about the role of STAT-5B in vessel wall remodeling, we examined its involvement in platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMC growth and motility and balloon injury-induced neointima formation. PDGF-BB activated STAT-5B as measured by its tyrosine phosphorylation, DNA binding, and reporter gene activity. PDGF-BB induced cyclin D1 expression, CDK4 activity, and Rb protein phosphorylation, leading to VSMC growth and motility, and these responses were suppressed by the blockade of STAT-5B. Increased cyclin D1 levels, CDK4 activity, and Rb protein phosphorylation were observed in 1-week balloon-injured arteries compared with uninjured arteries, and these responses were also suppressed by adenovirus-mediated expression of dnSTAT-5B. In addition, adenovirus-mediated expression of dnSTAT-5B attenuated balloon injury-induced smooth muscle cell migration from media to intima and their proliferation in intima, resulting in reduced neointima formation. These observations indicate that STAT-5B plays an important role in PDGF-BB-induced VSMC growth and motility in vitro and balloon injury-induced neointima formation in vivo.




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Copyright © 2007 by the American Society for Investigative Pathology.