Effects of substrate mechanics on angiogenic capacity and nitric oxide release in human endothelial cells
Effects of substrate mechanics on angiogenic capacity and nitric oxide release in human endothelial cells
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DOI：
10.1111/nyas.14326
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发表时间：
2020-06-01
影响因子：
5.2
通讯作者：
Seyedjafari, Ehsan
中科院分区：
文献类型：
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作者：
Jannatbabaei, Atefeh;Tafazzoli-Shadpour, Mohammad;Seyedjafari, Ehsan
血管弹性丧失是由于在衰老和某些疾病（包括动脉粥样硬化）的影响下，弹性动脉的细胞外基质进行性退化所致。为了研究血管壁硬化对内皮细胞 (EC) 功能的影响，我们将人脐静脉 EC 接种到不同柔顺性的聚二甲基硅氧烷基底上。当电镀在更柔顺的基板上时，EC 组装成毛细管状结构。相比之下，即使存在血管内皮生长因子（VEGF），它们也无法在坚硬的基质上形成网络。细胞增殖和迁移随着硬度的增加而增加，而内皮细胞在软基质上释放更多的一氧化氮 (NO)。 VEGF 治疗以硬度依赖性方式增加迁移和 NO 释放。细胞弹性的原子力显微镜测量以及肌动蛋白纤维分析表明，镀在更柔顺的表面上的 EC 在机械上更柔软，大部分肌动蛋白呈弥散排列。我们的结果表明，基质硬化会诱导肌动蛋白重组，这可以通过 EC 中的皮质硬化来反映，这可能会导致其血管生成能力和 NO 释放减少。因此，EC 的机械特性显示出预后和治疗潜力，并可能作为血管功能的可靠生物标志物。
Loss of vascular elasticity results from progressive degeneration of the extracellular matrix of elastic arteries under the effect of aging and certain diseases, including atherosclerosis. To investigate the influence of vessel wall stiffening on endothelial cell (EC) function, we seeded human umbilical vein ECs onto variably compliant polydimethylsiloxane substrates. When plated on the more compliant substrate, ECs assembled into capillary-like structures. By contrast, they failed to form a network on stiff substrates, even in the presence of vascular endothelial growth factor (VEGF). Cell proliferation and migration increased with stiffness, while ECs released more nitric oxide (NO) on the soft substrate. Treatment with VEGF increased migration and NO release in a stiffness-dependent manner. Atomic force microscopy measurement of cell elasticity along with actin fiber analysis revealed that ECs plated on the more compliant surface were mechanically softer, with mostly diffuse actin arrangement. Our results demonstrate that matrix stiffening induces actin reorganizations, reflected by cortical stiffening in ECs, which may lead to a decrease in their angiogenic capacity and NO release. Hence, the mechanical properties of ECs display a prognostic and therapeutic potential and might serve as a reliable biomarker of vascular function.