Platelet-derived microparticles augment the adhesion and neovascularization capacities of circulating angiogenic cells obtained from atherosclerotic patients
Platelet-derived microparticles augment the adhesion and neovascularization capacities of circulating angiogenic cells obtained from atherosclerotic patients
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DOI：
10.1016/j.atherosclerosis.2013.01.040
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发表时间：
2013-04-01
期刊：
影响因子：
5.3
通讯作者：
Imaizumi, Tsutomu
中科院分区：
文献类型：
--
作者：
Ohtsuka, Masanori;Sasaki, Ken-ichiro;Imaizumi, Tsutomu
目的：动脉粥样硬化患者循环血管生成细胞（CACs）的新生血管形成相关能力受损，这可能解释了动脉粥样硬化患者源性CACs治疗性血管生成效果不理想的原因。血小板衍生的微粒（PMP）被报道增加CAC的再内皮化能力。因此，我们调查是否PMPs可以增加动脉粥样硬化患者衍生的CACs在体外和体内的新血管形成相关的能力，如果是这样的话，相关的mechanism.Methods和结果：我们从动脉粥样硬化患者衍生的外周血中分离出单核细胞和PMPs，并通过单核细胞和PMPs的共培养产生PMP预处理的CACs（PMP-CACs）。虽然PMP-CACs的迁移能力与CACs相似，但PMP-CACs的粘附能力更强。PMPs向培养液中释放RANTES，RANTES受体在CACs和PMP-CACs表面表达相似。大鼠后肢缺血后静脉注射PMP-CACs比注射CACs更能促进缺血肢体的新生血管形成。PMP-CACs掺入缺血肢体毛细血管的数量多于掺入的CACs。结论：PMP分泌的RANTES可能在增强CACs的粘附和新生血管能力中发挥作用。注射PMP-CACs可能是一种新的策略，以增强动脉粥样硬化患者肢体缺血的治疗性血管生成的效果。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Objective: The neovascularization-related capacities of circulating angiogenic cells (CACs) are impaired in atherosclerotic patients, which may explain the unsatisfactory effects of therapeutic angiogenesis with atherosclerotic patient-derived CACs. Platelet-derived microparticles (PMPs) were reported to augment the re-endothelialization capacity of CACs. Accordingly, we investigated whether PMPs could augment the neovascularization-related capacities of atherosclerotic patient-derived CACs in vitro and in vivo and if so, the associated mechanisms.Methods and results: We isolated mononuclear cells and PMPs from atherosclerotic patient-derived peripheral blood and generated PMP-pretreated CACs (PMP-CACs) by co-culture of the mononuclear cells and PMPs. Although the migration capacity of PMP-CACs was similar to that of CACs, the adhesion capacity of PMP-CACs was greater. PMPs released RANTES into the culture medium, and the receptors were similarly expressed on the surfaces of CACs and PMP-CACs. Intravenous injection of PMP-CACs to rats with hindlimb ischemia augmented neovascularization of the ischemic limbs more than the injection of CACs. The number of PMP-CACs incorporated into the capillaries of the ischemic limbs was greater than that of incorporated CACs. The augmented adhesion and neovascularization capacities by PMP-CACs were canceled out by a RANTES neutralizing antibody.Conclusions: PMP-secreted RANTES may play a role in the augmenting adhesion and neovascularization capacities of CACs. Injection of PMP-CACs may be a new strategy to augment the effects of therapeutic angiogenesis for limb ischemia in atherosclerotic patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved.