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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Disruption of nrf2 signaling impairs angiogenic capacity of endothelial cells: implications for microvascular aging.
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Disruption of nrf2 signaling impairs angiogenic capacity of endothelial cells: implications for microvascular aging.

机译：NRF2信号传导的破坏损害内皮细胞的血管生成能力：对微血管衰老的影响。

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The redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2) plays a key role in preserving a healthy endothelial phenotype and maintaining the functional integrity of the vasculature. Previous studies demonstrated that aging is associated with Nrf2 dysfunction in endothelial cells, which alters redox signaling and likely promotes the development of large vessel disease. Much less is known about the consequences of Nrf2 dysfunction at the level of the microcirculation. To test the hypothesis that Nrf2 regulates angiogenic capacity of endothelial cells, we determined whether disruption of Nrf2 signaling (by siRNA knockdown of Nrf2 and overexpression of Keap1, the cytosolic repressor of Nrf2) impairs angiogenic processes in cultured human coronary arterial endothelial cells stimulated with vascular endothelial growth factor and insulin-like growth factor-1. In the absence of functional Nrf2, coronary arterial endothelial cells exhibited impaired proliferation and adhesion to vitronectin and collagen. Disruption of Nrf2 signaling also reduced cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing technology) and impaired the ability of coronary arterial endothelial cells to form capillary-like structures. Collectively, we find that Nrf2 is essential for normal endothelial angiogenic processes, suggesting that Nrf2 dysfunction may be a potential mechanism underlying impaired angiogenesis and microvascular rarefaction in aging.
机译：氧化还原敏感转录因子NF-E2相关因子2（NRF2）在保留健康内皮表型并保持脉管系统的功能完整性方面起着关键作用。以前的研究表明，老化与内皮细胞中的NRF2功能障碍有关，其改变了氧化还原信号，并且可能促进大容器病的发展。关于在微循环水平下NRF2功能障碍的后果所知的更少。为了测试NRF2调节内皮细胞血管生成能力的假设，我们确定了NRF2信号传导的破坏（通过NRF2的胚胎敲低，Keap1的过表达，NRF2的胞质阻遏物）损害血管培养的人冠状动脉内皮细胞中的血管生成过程内皮生长因子和胰岛素样生长因子-1。在没有功能性NRF2的情况下，冠状动脉内皮细胞表现出对VITRONECTIN和胶原蛋白的增殖和粘附性受损。 NRF2信号传导的破坏也降低了细胞迁移（通过使用电池 - 基质阻抗传感技术通过伤口愈合测定测量），并损害冠状动脉内皮细胞形成毛细管状结构的能力。总的来说，我们发现NRF2对于正常内皮血管生成过程至关重要，表明NRF2功能障碍可以是血管生成受损和衰老微血管稀释剂的潜在机制。

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