Pravastatin Induces Rat Aortic Endothelial Cell Proliferation and Migration via Activation of PI3K/Akt/mTOR/p70 S6 Kinase Signaling

• Nakao Takafumi

  Department of Pharmacology, Osaka City University Medical School, Japan

• Shiota Masayuki

  Department of Pharmacology, Osaka City University Medical School, Japan

• Tatemoto Yasuyoshi

  Department of Pharmacology, Osaka City University Medical School, Japan

• Izumi Yasukatsu

  Department of Pharmacology, Osaka City University Medical School, Japan

• Iwao Hiroshi

  Department of Pharmacology, Osaka City University Medical School, Japan

抄録

The HMG-CoA reductase inhibitors (statins) have been shown to exert several vascular protective effects that are not related to changes in cholesterol profile, and these effects of statins are partly caused by the activation of angiogenesis. Endothelial cell (EC) proliferation and migration are crucial events for angiogenesis and statins are known to enhance these events. However, the molecular mechanism by which statins promote EC proliferation and migration is not fully understood. In this study, we show Akt and its downstream target mammalian target of rapamycin (mTOR) play an important role in pravastatin-induced EC proliferation and migration. We found that pravastatin significantly enhanced the proliferation and migration of rat aortic endothelial cells (rAECs). The addition of pravastatin to rAECs resulted in rapid phosphorylation of Akt and p70 S6 kinase (p70S6K). LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), blocked both Akt and p70S6K phosphorylation, whereas rapamycin, a specific inhibitor of mTOR, suppressed only p70S6K phosphorylation induced by pravastatin. Furthermore, both LY294002 and rapamycin inhibited pravastatin-induced rAEC proliferation and migration. Taken together, our findings indicate that pravastatin activates PI3K/Akt/mTOR /p70S6K signaling in this sequential manner and this pathway contributes to pravastatin-induced rAEC proliferation and migration.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 105 (4), 334-341, 2007

  公益社団法人 日本薬理学会

キーワード

• pravastatin
• endothelial cell
• Akt
• mammalian target of rapamycin (mTOR)
• p70 S6 kinase

詳細情報

• CRID: 1390282680157764480
• NII論文ID: 10024317024
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.fp0070682
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 9314399
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9314399
• Web Site: https://search.jamas.or.jp/link/ui/2008155491
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可