FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs.
FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs.
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DOI：
10.1371/journal.pone.0092626
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Imaizumi T
中科院分区：
文献类型：
--
作者：
Nakayoshi T;Sasaki K;Kajimoto H;Koiwaya H;Ohtsuka M;Ueno T;Chibana H;Itaya N;Sasaki M;Yokoyama S;Fukumoto Y;Imaizumi T
通过肌肉注射早期促血管生成细胞（EPCs）到缺血肢体的治疗性血管生成的效果不令人满意。缺血肢体中的氧化应激可能加速注射的EPCs的凋亡，导致较少的新血管形成。叉头转录因子4（FOXO 4）在氧化应激诱导内皮祖细胞凋亡信号通路中起重要作用。因此，我们评估了FOXO 4敲低EPCs（FOXO 4 KD-EPCs）是否可以抑制氧化应激诱导的细胞凋亡，并增加缺血肢体的新生血管能力。我们转染了针对FOXO 4的人EPCs的小干扰RNA，以产生FOXO 4KD-EPCs，并证实成功敲除。FOXO 4KD-EPCs在体外抗过氧化氢诱导的细胞凋亡。免疫缺陷大鼠缺血肢体组织的氧化应激反应强于非缺血肢体组织。虽然注射到大鼠缺血肢体中的凋亡EPCs的数量大于注射到大鼠非缺血肢体中的凋亡EPCs的数量，但注射到大鼠缺血肢体中的FOXO 4KD-EPCs比EPCs带来更少的凋亡和更多的新血管形成。两者合计，使用FOXO 4KD-EPCs与抗氧化应激诱导的凋亡可能是一个新的策略，以增加治疗血管生成的EPCs肌肉注射的效果。
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.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
5
作者：
Urbich, Carmen;De Souza, Ayesha I.;Mayr, Manuel
通讯作者：
Mayr, Manuel
影响因子：
1.5
作者：
Alves, Wellington Forte;Aguiar, Erika Elisa;de Vasconcelos, Paulo Roberto Leitao
通讯作者：
de Vasconcelos, Paulo Roberto Leitao
影响因子：
3.3
作者：
Saito, Yutaka;Sasaki, Ken-ichiro;Imaizumi, Tsutomu
通讯作者：
Imaizumi, Tsutomu
DOI：
10.1161/circinterventions.108.799361
发表时间：
2009-06-01
影响因子：
5.6
作者：
Moriya, Junji;Minamino, Tohru;Komuro, Issei
通讯作者：
Komuro, Issei