Decreased vascular lesion formation in mice with inducible endothelial-specific expression of protein kinase Akt

Yasushi Mukai, Yoshiyuki Rikitake, Ichiro Shiojima, Sebastian Wolfrum, Minoru Satoh, Kyosuke Takeshita, Yukio Hiroi, Salvatore Salomone, Hyung Hwan Kim, Laura E. Benjamin, Kenneth Walsh, James K. Liao

研究成果: Contribution to journalArticle査読

68 被引用数 (Scopus)

抄録

To determine whether endothelial Akt could affect vascular lesion formation, mutant mice with a constitutively active Akt transgene, which could be inducibly targeted to the vascular endothelium using the tet-off system (EC-Akt Tg mice), were generated. After withdrawal of doxycycline, EC-Akt Tg mice demonstrated increased endothelial-specific Akt activity and NO production. After blood flow cessation caused by carotid artery ligation, neointimal formation was attenuated in induced EC-Akt Tg mice compared with noninduced EC-Akt Tg mice and control littermates. To determine the role of eNOS in mediating these effects, mice were treated with Nω-nitro-L- arginine methyl ester (L-NAME). Neointimal formation was attenuated to a lesser extent in induced EC-Akt Tg mice treated with L-NAME, suggesting that some of the vascular protective effects were NO independent. Indeed, endothelial activation of Akt resulted in less EC apoptosis in ligated arteries. Immunostaining demonstrated decreased inflammatory and proliferative changes in induced EC-Akt Tg mice after vascular injury. These findings indicate that endothelial activation of Akt suppresses lesion formation via increased NO production, preservation of functional endothelial layer, and suppression of inflammatory and proliferative changes in the vascular wall. These results suggest that enhancing endothelial Akt activity alone could have therapeutic benefits after vascular injury.

本文言語英語
ページ(範囲)334-343
ページ数10
ジャーナルJournal of Clinical Investigation
116
2
DOI
出版ステータス出版済み - 2 1 2006

All Science Journal Classification (ASJC) codes

  • 医学(全般)

フィンガープリント

「Decreased vascular lesion formation in mice with inducible endothelial-specific expression of protein kinase Akt」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル