Delivery of TFPI-2 using SonoVue and adenovirus results in the suppression of thrombosis and arterial re-stenosis

Delivery of TFPI-2 using SonoVue and adenovirus results in the suppression of thrombosis and arterial re-stenosis
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使用 SonoVue 和腺病毒递送 TFPI-2 可抑制血栓形成和动脉再狭窄。

DOI:
10.1258/ebm.2010.010046
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发表时间:
2010-09-01
影响因子:
3.2
通讯作者:
Chen, Juan
Chen, Juan
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Yuxue;Zhou, Jie;Chen, Juan

文献摘要

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基因可以用来治疗动脉粥样硬化。关键的问题是如何通过自由流动的血液中的动脉壁靶向一个基因。TFPI-2抑制血栓形成和动脉再狭窄,这表明其在动脉粥样硬化基因治疗中的潜在功能。微泡超声造影剂广泛应用于诊断成像,可用于将基因转移到动脉。通过使用SonoVue(一种微泡超声造影剂)将TFPI-2转染到动脉中,我们发现TFPI-2是体内抑制血管内皮细胞增殖的有效因子。与腺病毒相比,SonoVue具有相似的基因转染效率,但后者在体外和体内高表达TFPI-2蛋白,对血栓形成和动脉再狭窄的抑制作用更强。将基因转染到动脉壁时,SonoVue的损伤较小。这些数据表明,将人TFPI-2转染到动脉壁上可以抑制血栓形成和动脉再狭窄,减少动脉粥样硬化。
Genes could be used to treat atherosclerosis. The key problem is how to target a gene through the walls of arteries in free-flowing blood. TFPI-2 has been shown to suppress thrombosis and arterial re-stenosis, which indicates its potential function in gene therapy for atherosclerosis. The microbubble ultrasound contrast agent is widely applied in diagnostic imaging, and could be used for transferring genes into arteries. By transfecting TFPI-2 into arteries using SonoVue (a kind of microbubble ultrasound contrast agent), we identified TFPI-2 as an available factor for inhibiting the proliferation of vascular endothelial cells in vivo. Compared with adenovirus, SonoVue showed similar gene transfection efficiency, but the latter showed stronger inhibition of thrombosis and arterial re-stenosis with a high expression of TFPI-2 protein in vitro and in vivo. SonoVue was less damaging when transfecting genes into the arterial wall. These data indicate that transfecting human TFPI-2 into the arterial wall may suppress thrombosis and arterial re-stenosis, and reduce atherosclerosis.