Evaluation of endothelial cell culture as a model system of vascular ageing
Evaluation of endothelial cell culture as a model system of vascular ageing
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DOI：
10.1016/j.exger.2010.06.003
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发表时间：
2010-10-01
影响因子：
3.9
通讯作者：
Kristensen, Peter
中科院分区：
文献类型：
--
作者：
Boisen, Louise;Drasbek, Kim Ryun;Kristensen, Peter
本研究的目的是评估长期内皮细胞培养作为血管老化模型系统的相关性。微血管内皮细胞和大血管内皮细胞连续传代直至复制衰老，并在其整个生命周期中评估它们在基质胶上培养时形成管状结构的能力。对于这两种细胞类型，低传代培养物采用均质的鹅卵石形态，而衰老培养物则极其异质。此外，两种细胞类型都显示出管形成能力随着体外老化而降低，这与体内老化时观察到的血管生成潜力的降低一致。对衰老相关的β-半乳糖苷酶活性的检查显示，与塑料上培养的细胞相比，形成管的细胞的活性增加，这可能归因于正在形成管的细胞的溶酶体含量增加。由于这种衰老相关的β-半乳糖苷酶活性的增加与细胞的复制年龄无关，因此衰老相关的β-半乳糖苷酶活性可能不是分化内皮细胞的相关衰老标志物。与年龄相关的管形成能力的降低表明内皮细胞的长期培养可能是血管老化的有效模型系统，这使其成为高通量筛选影响血管生成的化合物的理想平台。 (C) 爱思唯尔公司。保留所有权利。
The purpose of this study was to evaluate the relevance of long-term endothelial cell culture as a model system of vascular ageing. Micro- and macrovascular endothelial cells were serially passaged until replicative senescence and their ability to form tube-like structures when cultured on Matrigel was assessed throughout their lifespan. For both cell types low passage cultures adopted a homogeneous cobblestone morphology, while senescent cultures were extremely heterogeneous. Furthermore, both cell types showed a reduction in tube formation ability with in vitro ageing, which is in accordance with the reduction in angiogenic potential observed with ageing in vivo. Examination of senescence associated beta-galactosidase activity revealed an increased activity in cells forming tubes as compared to cells cultured on plastic, which could be attributed to an increased lysosomal content of cells undergoing tube formation. As this increased senescence associated beta-galactosidase activity was unrelated to the replicative age of the cells, senescence associated beta-galactosidase activity may not be a relevant senescence marker for differentiating endothelial cells. The age-related reduction in tube formation ability suggested that long-term culture of endothelial cells may be a valid model system of vascular ageing, which makes it an ideal platform for high throughput screening of compounds influencing angiogenesis. (C) Elsevier Inc. All rights reserved.