Ultrasound stimulation restores impaired neovascularization-related capacities of human circulating angiogenic cells
Ultrasound stimulation restores impaired neovascularization-related capacities of human circulating angiogenic cells
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DOI：
10.1093/cvr/cvs173
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发表时间：
2012-09-01
影响因子：
10.8
通讯作者：
Imaizumi, Tsutomu
中科院分区：
文献类型：
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作者：
Toyama, Yasuyuki;Sasaki, Ken-ichiro;Imaizumi, Tsutomu
治疗性血管生成在严重肢体缺血中的不满意效果可能归因于使用来自动脉粥样硬化患者的循环血管生成细胞（CAC），这些患者具有受损的新生血管形成相关能力。为了验证超声刺激是否能恢复受损的细胞功能，我们在培养人外周血单个核细胞4d以获得CACs的过程中，每天用低强度脉冲超声刺激（LIPUS）刺激培养中的细胞。LIPUS应用于健康志愿者培养的细胞增强了CACs的生成和迁移能力，增加了培养基中血管生成素2和氮氧化物的浓度，并增加了磷酸化Akt和内皮型一氧化氮合酶在CACs中的表达。LIPUS应用于动脉粥样硬化患者的培养细胞也增强了CAC的生成和迁移能力。尽管与健康志愿者来源的CACs相比，动脉粥样硬化患者来源的CACs肌肉注射后，裸鼠缺血后肢的新血管形成受到损害，但动脉粥样硬化患者来源的培养细胞的LIPUS恢复了新血管形成能力，LIPUS预处理的CACs的治疗性血管生成可能是挽救动脉粥样硬化患者严重肢体缺血的新策略。
Unsatisfactory effects of therapeutic angiogenesis in critical limb ischaemia may be ascribed to use of circulating angiogenic cells (CACs) derived from atherosclerotic patients with impaired neovascularization-related capacities. We tested whether ultrasound cell stimulation can restore the impaired capacities.During culture of human peripheral blood-derived mononuclear cells for 4days to achieve CACs, we stimulated the cells in culture daily with low-intensity pulsed ultrasound stimulation (LIPUS). Application of LIPUS to cells in culture derived from healthy volunteers augmented the generation and migration capacities of CACs, increased concentrations of angiopoietin 2 and nitrogen oxides in the culture medium, and increased the expression of phosphorylated-Akt and endothelial nitric oxide synthase in CACs on western blotting. Application of LIPUS to cells in culture derived from atherosclerotic patients also augmented the generation and migration capacities of CACs. Although neovascularization in the ischaemic hindlimb of athymic nude mice was impaired after intramuscular injection of CACs derived from atherosclerotic patients compared with that using CACs derived from healthy volunteers, LIPUS of the cells in culture derived from atherosclerotic patients restored the neovascularization capacities.Therapeutic angiogenesis with LIPUS-pre-treated CACs may be a new strategy to rescue critical limb ischaemia in atherosclerotic patients.