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. 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 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.

journal_name

Circulation

journal_title

Circulation

authors

Tokunou T,Shibata R,Kai H,Ichiki T,Morisaki T,Fukuyama K,Ono H,Iino N,Masuda S,Shimokawa H,Egashira K,Imaizumi T,Takeshita A

doi

10.1161/01.CIR.0000085164.13439.89

subject

Has Abstract

pub_date

2003-09-09 00:00:00

pages

1246-52

issue

10

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000085164.13439.89

journal_volume

108

pub_type

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