title: Apoptosis induced by inhibition of cyclic AMP response element-binding protein in vascular smooth muscle cells.
abstract: BACKGROUND
  The balance between apoptosis and proliferation of vascular smooth muscle cells (VSMCs) is believed to contribute to the vascular remodeling process. Cyclic AMP response element-binding protein (CREB) is a critical transcription factor for the survival of neuronal cells and T lymphocytes. However, the role of CREB in blood vessels is incompletely characterized.
  
  
  RESULTS
  Nuclear staining with Hoechst 33258 or propidium iodine showed an increase in apoptotic cells with activation of caspase-3 in VSMCs infected with adenovirus expressing the dominant-negative form of CREB (AdCREBM1). Basal expression of Bcl-2 and Bcl-2 promoter activity were decreased by infection with AdCREBM1. Immunohistochemistry revealed that CREB was mainly induced and activated in the neointimal alpha-smooth muscle actin-positive cells of rat carotid artery after balloon injury. Infection with AdCREBM1 suppressed neointimal formation (intima-media ratio) by 33.8% after 14 days of injury, which was accompanied by an increase in apoptosis as indicated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells and a decrease in bromodeoxyuridine incorporation.
  
  
  CONCLUSIONS
  These results suggest that CRE-dependent gene transcription might play an important role in the survival and proliferation of VSMCs. CREB might be a novel transcription factor mediating the vascular remodeling process and a potential therapeutic target for atherosclerotic disease.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan.
authors.forename: Tomotake
authors.initials: T
authors.lastname: Tokunou
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kai
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ichiki
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Kae
authors.initials: K
authors.lastname: Fukuyama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ono
authors.forename: Naoko
authors.initials: N
authors.lastname: Iino
authors.forename: Satoko
authors.initials: S
authors.lastname: Masuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D005799:Genes, Dominant; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D014162:Transfection; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D001973:Bromodeoxyuridine