Apoptosis induced by inhibition of cyclic AMP response element-binding protein in vascular smooth muscle cells

Tomotake Tokunou, Rei Shibata, Hisashi Kai, Toshihiro Ichiki, Takashi Morisaki, Kae Fukuyama, Hiroki Ono, Naoko Iino, Satoko Masuda, Hiroaki Shimokawa, Kensuke Egashira, Tsutomu Imaizumi, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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. Methods and 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 α-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.

Original languageEnglish
Pages (from-to)1246-1252
Number of pages7
Issue number10
Publication statusPublished - Sept 9 2003

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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