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

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. (Am J

Cyclin D1 Is a Bona Fide Target Gene of NFATc1 and Is Sufficient in the Mediation of Injury-induced Vascular Wall Remodeling

“…2A regulation, cyclin D1 has been reported to play a role in cell migration (32). In this aspect, we recently reported that STAT-5B-dependent expression of cyclin D1 plays a role in PDGF-BBinduced VSMC migration (24,33). Because NFATc1 plays a role in PDGF-BB-induced HASMC DNA synthesis and migration, and it mediates PDGF-BB-induced cyclin D1 expression, we were intrigued to find whether cyclin D1 has any role in HASMC migration downstream of NFATc1.…”

“…CDK4 Assay-Protein extracts from cells or tissues were analyzed for CDK4 activity as described previously (24). The 32 Plabeled Rb protein was visualized by autoradiography, and the band intensities were quantified using NIH Image J.…”

Nuclear Factor of Activated T Cells c1 Mediates p21-activated Kinase 1 Activation in the Modulation of Chemokine-induced Human Aortic Smooth Muscle Cell F-actin Stress Fiber Formation, Migration, and Proliferation and Injury-induced Vascular Wall Remodeling

“…CDK4/6 and Pak1 Assays-Cell extracts were analyzed for CDK4/6 and/or Pak1 activities as described previously (26,27). The […”

“…DNA Synthesis-DNA synthesis was measured by [ 3 H]thymidine incorporation as described previously and expressed as counts/min/dish (26).…”

“…Western Blot Analysis-Cell or tissue extracts containing an equal amount of protein from the control and each treatment/ condition were analyzed by Western blotting for the indicated molecule using its specific antibody as described previously (26). The band intensities were quantified using National Institutes of Health ImageJ.…”