Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction
Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction
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DOI：
10.1111/j.1440-1681.2004.04022.x
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发表时间：
2004-07-01
影响因子：
2.9
通讯作者：
Nishio, I
中科院分区：
文献类型：
--
作者：
Imanishi, T;Hano, T;Nishio, I
1.最近的研究表明，冠状动脉危险因素与骨髓来源的内皮祖细胞（EPC）的数量和功能之间存在关联。我们研究了氧化低密度脂蛋白（ox-LDL）对EPC衰老的影响，导致细胞功能障碍.从人外周血中分离内皮祖细胞并进行表征。暴露培养的EPC氧化低密度脂蛋白（10 μ g/mL）显着加速衰老的速度相比，在20天的文化中确定的酸性β-半乳糖苷酶染色的控制。凝集素样氧化低密度脂蛋白受体-1（LOX-1）抗体（Ab）或阿托伐他汀预处理均能显著抑制氧化低密度脂蛋白诱导的EPC衰老（P < 0.01）.由于细胞衰老是由端粒酶，延长端粒的关键影响，我们测量端粒酶活性，使用聚合酶链反应-ELISA为基础的测定。氧化低密度脂蛋白显著降低端粒酶活性至约50%，LOX-1抗体或阿托伐他汀预处理可显著消除该作用（P < 0.01）。我们研究了ox-LDL诱导的EPC衰老是否转化为EPC功能障碍。MTS试验显示ox-LDL对EPC增殖有抑制作用。在基质胶分析中，与对照组相比，ox-LDL处理的EPC参与网络形成的可能性更小.结论：ox-LDL可加速内皮细胞衰老，其机制可能与端粒酶失活有关。氧化LDL诱导的EPC衰老导致增殖能力和网络形成受损。
1. Recent studies have revealed an association between coronary risk factors and both the number and function of bone marrow-derived endothelial progenitor cells (EPC). We investigated the effect of oxidized low-density lipoprotein (ox-LDL) on the senescence of EPC, leading to cellular dysfunction.2. Endothelial progenitor cells were isolated from human peripheral blood and characterized. The exposure of cultured EPC to ox-LDL (10 mug/mL) significantly accelerated the rate of senescence compared with control during 20 days in culture as determined by acidic beta-galactosidase staining. Oxidized LDL-induced EPC senescence was significantly inhibited by pretreatment with either lectin-like ox-LDL receptor-1 (LOX-1) antibody (Ab) or atorvastatin (P < 0.01).3. Because cellular senescence is critically influenced by telomerase, which elongates telomeres, we measured telomerase activity using a polymerase chain reaction-ELISA-based assay. Oxidized LDL significantly diminished telomerase activity to approximately 50%, an effect that was significantly abolished by pretreatment with either LOX-1 Ab or atorvastatin (P < 0.01).4. We examined whether ox-LDL-induced EPC senescence translates into EPC dysfunction. An MTS assay disclosed an inhibitory effect of ox-LDL on EPC proliferation. In a Matrigel assay, EPC treated with ox-LDL were less likely to participate in network fomation compared with controls.5. In conclusions, ox-LDL accelerates the onset of EPC senescence, which may be related to telomerase inactivation. Oxidized LDL-induced EPC senescence leads to the impairment of proliferative capacity and network formation.