on May 5, 2005
Published online before print May 5, 2005, doi: 10.1161/01.ATV.0000168902.18672.2f
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Submitted on September 29, 2004
Accepted on April 5, 2005
A Novel 
v
3 Integrin Antagonist Suppresses Neointima Formation for More Than 4 Weeks After Balloon Injury in Rats
Yayoi Honda *;
From the Dainippon Pharmaceutical Co., Ltd., Suita, Osaka, Japan.
* To whom correspondence should be addressed. E-mail: yayoi-honda{at}dainippon-pharm.co.jp.
Objectives--We performed a detailed kinetic analysis in a rat balloon injury model to clarify the essential roles of 
v
3 integrin and endothelial cell (EC) regeneration in neointima formation. Using this model, we evaluated the antistenotic effect of BS-1417, a novel v3 integrin antagonist.
Methods and Results--Kinetic analysis using RT-PCR showed that v3 integrin-related genes are upregulated before neointima formation. Morphological and functional analyses revealed that EC regeneration requires >4 weeks after injury, and that recovery of EC normal function coincides with the arrest of neointima formation. Subcutaneous infusion of BS-1417 for 2, 4, 7, or 12 weeks after injury potently inhibited neointima formation without affecting EC regeneration. Although withdrawal of treatment with BS-1417 after short-term administration after injury resulted in catch-up growth of neointima, a long-term study suggested that this catch-up growth can be prevented by continuous administration of BS-1417 until EC regeneration.
Conclusion--We clarified that v3 integrin and EC regeneration play an essential role in neointima formation, and that continuous administration of BS-1417 potently and stably inhibits neointima formation without affecting EC regeneration. These findings suggest that BS-1417 might be useful as a novel systemic drug for the treatment of restenosis.
Key words:
v3 integrin antagonist •
endothelial cell regeneration •
vascular smooth muscle •
gene expression •
rat balloon injury model
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