Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
Ann N Y Acad Sci. 2020 Jun;1470(1):31-43. doi: 10.1111/nyas.14326. Epub 2020 Mar 12.
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.
血管弹性的丧失是由于弹性动脉的细胞外基质在衰老和某些疾病（包括动脉粥样硬化）的影响下逐渐退化所致。为了研究血管壁僵硬对内皮细胞（EC）功能的影响，我们将人脐静脉内皮细胞接种到具有不同顺应性的聚二甲基硅氧烷基底上。当接种在顺应性更高的基底上时，EC 会组装成类似毛细血管的结构。相比之下，即使存在血管内皮生长因子（VEGF），它们也无法在刚性基底上形成网络。细胞增殖和迁移随硬度的增加而增加，而 EC 在软基底上释放更多的一氧化氮（NO）。VEGF 的处理以依赖于硬度的方式增加迁移和 NO 释放。沿 actin 纤维分析的细胞弹性原子力显微镜测量表明，接种在更顺应性表面上的 EC 更柔软，其 actin 排列主要是弥散的。我们的结果表明，基质变硬会诱导 actin 的重排，这反映在 EC 中的皮质变硬上，这可能导致其血管生成能力和 NO 释放减少。因此，EC 的力学性能具有预后和治疗潜力，并可能成为血管功能的可靠生物标志物。
