FoxO3a suppresses the senescence of cardiac microvascular endothelial cells by regulating the ROS-mediated cell cycle

Xu Feng Qi, Zhuo Ying Chen, Jing Bo Xia, Li Zheng, Hui Zhao, Long Quan Pi, Kyu Sang Park, Soo Ki Kim, Kyu Jae Lee, Dong Qing Cai

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

FoxO3a plays an important role in the aging process and decreases with age. However, the potential regulatory roles of FoxO3a in processes involved in cardiac microvascular endothelial cell (CMEC) senescence, and its underlying molecular mechanisms have not been elucidated. This study demonstrates that FoxO3a is deactivated in senescent CMECs together with the inhibition of proliferation and tube formation. Furthermore, the activation of the antioxidant enzymes catalase and SOD, downstream FoxO3a targets, was significantly decreased, thereby leading to cell cycle arrest in G1-phase by increased ROS generation and subsequently the activation of the p27Kip1 pathway. However, FoxO3a overexpression in primary low-passage CMECs not only significantly suppressed the senescence process by increasing the activation of catalase and SOD but also markedly inhibited ROS generation and p27Kip1 activation, although it failed to reverse cellular senescence. Moreover, both cell viability and tube formation were greatly increased by FoxO3a overexpression in primary CMECs during continuous passage. In addition, FoxO3a, deficiency in low-passage CMECs, accelerated the senescence process. Collectively, our data suggest that FoxO3a suppresses the senescence process in CMECs by regulating the antioxidant/ROS/p27Kip1 pathways, although it fails to reverse the cellular senescent phenotype.

Original languageEnglish
Pages (from-to)114-126
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume81
DOIs
Publication statusPublished - 2015 Apr 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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