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 journalArticle

12 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 1 2007

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beraprost
Vascular Smooth Muscle
Smooth Muscle Myocytes
Growth
Cyclic AMP-Dependent Protein Kinases
Synthetic Prostaglandins
DNA Nucleotidylexotransferase
Platelet-Derived Growth Factor
Epoprostenol
Protein Kinase Inhibitors
Adenoviridae
Thymidine
Small Interfering RNA
Transfection
Blood Vessels
Arteries
Western Blotting
Cell Proliferation
RNA
Apoptosis

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Ohtsubo, H., Ichiki, T., Miyazaki, R., Inanaga, K., Imayama, I., Hashiguchi, Y., ... Sunagawa, K. (2007). Inducible cAMP early repressor inhibits growth of vascular smooth muscle cell. Arteriosclerosis, thrombosis, and vascular biology, 27(7), 1549-1555. https://doi.org/10.1161/ATVBAHA.107.145011

Inducible cAMP early repressor inhibits growth of vascular smooth muscle cell. / Ohtsubo, Hideki; Ichiki, Toshihiro; Miyazaki, Ryohei; Inanaga, Keita; Imayama, Ikuyo; Hashiguchi, Yasuko; Sadoshima, Junichi; Sunagawa, Kenji.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 27, No. 7, 01.07.2007, p. 1549-1555.

Research output: Contribution to journalArticle

Ohtsubo, H, Ichiki, T, Miyazaki, R, Inanaga, K, Imayama, I, Hashiguchi, Y, Sadoshima, J & Sunagawa, K 2007, 'Inducible cAMP early repressor inhibits growth of vascular smooth muscle cell', Arteriosclerosis, thrombosis, and vascular biology, vol. 27, no. 7, pp. 1549-1555. https://doi.org/10.1161/ATVBAHA.107.145011
Ohtsubo, Hideki ; Ichiki, Toshihiro ; Miyazaki, Ryohei ; Inanaga, Keita ; Imayama, Ikuyo ; Hashiguchi, Yasuko ; Sadoshima, Junichi ; Sunagawa, Kenji. / Inducible cAMP early repressor inhibits growth of vascular smooth muscle cell. In: Arteriosclerosis, thrombosis, and vascular biology. 2007 ; Vol. 27, No. 7. pp. 1549-1555.
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