FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs

2013 Fiscal Year Final Research Report

• Project/Area Number: 23791509
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Kurume University
• Principal Investigator: NAKAYOSHI TAKAHARU 久留米大学, 医学部, 助教 (90511824)
• Project Period (FY): 2011 – 2013
• Keywords: 前血管新生細胞 / アポトーシス / 酸化ストレス / FOXO

Research Abstract

We assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs.
We transfected small interfering RNA (siRNA) targeted against FOXO4 to EPCs cultured from human peripheral mononuclear cells. In western blotting analyses, FOXO4 siRNA-transfected EPCs (FOXO4 KD -EPCs) showed 45% knockdown of FOXO4 and decreased expressions of pro-apoptotic proteins such as Bim and cleaved caspase-3. The FOXO4 knockdown significantly reduced the percentage of TUNEL-positive apoptotic EPCs induced by H2O2 in the flow cytometry analysis. Intramuscular injection of FOXO4 KD -EPCs to hind-limb ischemia rats significantly increased ischemic/non-ischemic hind-limb blood flow ratio and capillary density of the ischemic adductor muscle after 4 days compared to the injection of Nega-EPCs. FOXO4 KD -EPCs showed anti-apoptosis capacity, which may have contributed to neovascularization in ischemic tissues.

Research Products

• [Journal Article] FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization capacities in ischemic limbs (2014)
  • Author(s): Nakayoshi T, Sasaki K, Kajimoto H, Koiwaya H, Ohtsuka M, Ueno T, Chibana H, Itaya N, Sasaki M, Yokoyama S, Fukumoto Y, Imaizumi T.
  • Journal Title: PLoS One Volume: 24; 9 (3) Pages: e92626
  • DOI: 10.1371
  • Peer Reviewed
• [Presentation] FOXO4-knockdown augmented anti-apoptosis and neovascularization capacities of human early pro-angiogenic cells in rat ischemic limbs (2014)
  • Author(s): Takaharu Nakayoshi^1, Ken-ichiro Sasaki^1, Tsutomu Imaizumi^2, Takafumi Ueno^1, Hidemi Kajimoto^3, Hiroki Aoki^3, Shinji Yokoyama^1, Yasuyuki Toyama^1, Hiroshi Koiwaya^1, Masanori Ohtsuka^1, Yoshiaki Mitsutake^1, Naoki Itaya^1, Hidetoshi Chibana^1, and Yoshihiro Fukumoto ^1
  • Organizer: The 18^<th> Vascular Biology Meeting
  • Place of Presentation: Kyoto,Japan
  • Year and Date: 20140414-17
• [Presentation] Augmented Neovascularization Capacities of Endothelial Progenitors Cells via Anti-Apoptotic Effect by FOXO4 siRNA Transfection in Rats (2014)
  • Author(s): 仲吉孝晴、佐々木健一郎、上野高史、梶本英美、横山晋二、大塚昌紀、小岩屋宏、板家直樹、知花英俊、佐々木雅浩、今泉勉、福本義弘
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [Presentation] FOXO4-knockdown Augments Anti-apoptosis and Neovascularization Capacities of Human Early Endothelial Progenitors Cells (2013)
  • Author(s): 仲吉孝晴、佐々木健一郎、上野高史、梶本英美、横山晋二、大塚昌紀、小岩屋宏、板家直樹、知花英俊、今泉勉
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20130315-17
• [Presentation] FOXO4-knockdown Augmented Anti-apoptosis and Neovascularization Capacities of Atherosclerotic Patient-derived Circulating Angiogenic Cells (2013)
  • Author(s): Nakayoshi T,Sasaki K,Ueno T,Kajimoto H,Yokoyama S,Ohtsuka M,Koiwaya H, Itaya N,Tibana H,Imaizumi T
  • Organizer: The 19^<th > Asian Pacific Society of Cardiology 2013 Congress
  • Place of Presentation: Pattaya, Thailand
  • Year and Date: 20130221-24
• [Presentation] Augmented neovascularization capacities of circulating angiogenic cells via anti-apoptotic effect by FOXO4 siRNA transfection in rats (2012)
  • Author(s): 仲吉孝晴、佐々木健一郎、上野高史、梶本英美、青木浩樹、横山晋二、外山康之、小岩屋宏、大塚昌紀、光武良亮、板家直樹、知花英俊、今泉勉
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-04-14