Inducible cAMP early repressor inhibits growth of vascular smooth muscle cell

Hideki Ohtsubo, Toshihiro Ichiki, Ryohei Miyazaki, Keita Inanaga, Ikuyo Imayama, Yasuko Hashiguchi, Junichi Sadoshima, Kenji Sunagawa

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

OBJECTIVE - The role of inducible cAMP early repressor (ICER), a transcriptional repressor, in the vascular remodeling process has not been determined. We examined whether ICER affects growth of vascular smooth muscle cells (VSMCs). METHODS AND RESULTS - Semi-quantitative RT-PCR and Western blot analysis showed that expression of ICER was increased in beraprost (a prostaglandin I2 analogue)-stimulated VSMCs in a time- and dose-dependent manner. The induction of ICER was inhibited by pretreatment with H89, a protein kinase A (PKA) inhibitor, suggesting that PKA mediates the induction of ICER expression. Beraprost suppressed platelet-derived growth factor-induced thymidine incorporation in VSMCs, which was reversed by transfection of short interfering RNA for ICER, not by scramble RNA. Overexpression of ICER by an adenovirus vector attenuated neointimal formation (intima/media ratio) by 50% compared with overexpression of LacZ. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells was increased and the number of Ki-67-positive cells was decreased in ICER-transduced artery. CONCLUSION - These results suggest that ICER induces apoptosis and inhibits proliferation of VSMCs, and plays a critical role in beraprost-mediated suppression of VSMC proliferation. ICER may be an important endogenous inhibitor of vascular proliferation.

Original languageEnglish
Pages (from-to)1549-1555
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume27
Issue number7
DOIs
Publication statusPublished - Jul 2007

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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