Suppression of activation of signal transducer and activator of transcription-5B signaling in the vessel wall reduces balloon injury-induced neointima formation.
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.
Kundumani-Sridharan
Venkatesh
V
Department of Physiology, The University of Tennessee Health Science Center, 894 Union Ave., Memphis, TN 38163, USA.
Wang
Dong
D
Karpurapu
Manjula
M
Liu
Zhimin
Z
Zhang
Chunxiang
C
Dronadula
Nagadhara
N
Rao
Gadiparthi N
GN
D000818:Animals; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology*; D002404:Catheterization; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D017539:Tunica Intima / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D017540:Tunica Media / Q000166:cytology