Journal article
FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs
PloS one, Vol.9(3), p.e92626
03/24/2014
DOI: 10.1371/journal.pone.0092626
PMCID: PMC3963928
PMID: 24663349
Abstract
The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, 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 targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs.
Details
- Title: Subtitle
- FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs
- Creators
- Takaharu Nakayoshi - Kurume UniversityKen-Ichiro SasakiHidemi Kajimoto - Kurume UniversityHiroshi Koiwaya - Kurume UniversityMasanori Ohtsuka - Kurume UniversityTakafumi Ueno - Kurume UniversityHidetoshi Chibana - Kurume UniversityNaoki Itaya - Kurume UniversityMasahiro Sasaki - Kurume UniversityShinji Yokoyama - Kurume UniversityYoshihiro Fukumoto - Kurume UniversityTsutomu Imaizumi - Fukuoka International University
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(3), p.e92626
- DOI
- 10.1371/journal.pone.0092626
- PMID
- 24663349
- PMCID
- PMC3963928
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Language
- English
- Date published
- 03/24/2014
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984961028902771
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