Document Detail

Critical role of inducible costimulator signaling in the development of arteriosclerosis.
MedLine Citation:
PMID:  16990558     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Proliferation and migration of smooth muscle cells (SMCs) and migration and accumulation of monocytes and T cells are landmark events in the development of arteriosclerosis. SMC proliferation in the intima induces interruption of blood flow and results in ischemia and graft rejection. Inducible costimulator (ICOS) is a major costimulator of T cell activation. However, the effect of costimulatory molecules on the formation of neointimal hyperplasia has not been fully elucidated. We examined the role of the ICOS pathway in SMC proliferation. METHODS AND RESULTS: ICOS ligand (ICOSL) was detected in SMCs stimulated by interleukin (IL)-1beta, and coculture of stimulated SMCs and activated T cells induced SMC proliferation. Inhibition of the ICOS pathway resulted in inhibition of SMC proliferation. In models of transplantation and vascular injury, ICOSL was induced in SMCs in the neointima. Expression of IL-1beta, a key inducer of ICOSL expression, was significantly reduced in mice treated with anti-ICOS antibody or soluble form of ICOS (ICOSIg) and in ICOS-deficient mice. Inhibition of the ICOS pathway significantly suppressed neointimal thickening. CONCLUSIONS: These results indicate that ICOS on activated T cells contributes to neointimal formation through the regulation of SMC proliferation. These findings provide insights into new therapeutic strategies for arteriosclerosis.
Hisanori Kosuge; Jun-ichi Suzuki; Go Haraguchi; Noritaka Koga; Yasuhiro Maejima; Manabu Inobe; Mitsuaki Isobe; Toshimitsu Uede
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-21
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  26     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2006-12-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2660-5     Citation Subset:  IM    
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
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MeSH Terms
Antigens, Differentiation, T-Lymphocyte / genetics,  metabolism*
Arteriosclerosis / etiology*,  genetics,  metabolism*,  pathology
Cell Communication / drug effects,  physiology
Cell Proliferation*
Coculture Techniques
Gene Expression Regulation / drug effects,  physiology
Hyperplasia / pathology
Interleukin-1beta / pharmacology
Mice, Inbred C57BL
Mice, Knockout
Muscle, Smooth, Vascular / drug effects,  metabolism*,  pathology
T-Lymphocytes / cytology,  drug effects,  metabolism
Reg. No./Substance:
0/Antigens, Differentiation, T-Lymphocyte; 0/Interleukin-1beta; 0/inducible T-cell co-stimulator

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