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Activation of signal transducer and activator of transcription‐5B in the vessel wall by balloon injury leads to cyclin D1 upregulation and neointima formation
Author(s) -
Sridharan Venkatesh Kundumani,
Wang Dong,
Zhang Chunxiang,
Dronadula Nagadhara,
Rao Gadiparthi N
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1442-b
Subject(s) - neointima , cyclin d1 , tyrosine phosphorylation , stat protein , platelet derived growth factor receptor , microbiology and biotechnology , phosphorylation , stat3 , chemistry , stat , growth factor , cancer research , cell cycle , restenosis , biology , medicine , apoptosis , receptor , stent , biochemistry
Previously, we have demonstrated that STAT‐5B plays a role in thrombin‐induced VSMC growth and motility. In order to learn more about the role of STAT‐5B in vessel wall remodeling, here we have studied its involvement in platelet‐derived growth factor‐BB (PDGF‐BB)‐stimulated VSMC growth 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 these responses were suppressed by the blockade of STAT‐5B. Increased cyclin D1 levels, CDK4 activity, Rb protein phosphorylation and PCNA expression were observed in 1 week balloon‐injured arteries compared to 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 neointima formation. Together, these observations indicate that STAT‐5B plays an important role in vessel wall remodeling in response to injury.