Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2020-11-16 , DOI: 10.1016/j.bbagen.2020.129796 Nanyoung Yoon , Seunggyu Kim , Hye Kyoung Sung , Thanh Q. Dang , Jessie S. Jeon , Gary Sweeney
Background
Iron excess is a risk factor for cardiovascular diseases and it is important to understand the effect of iron on vascular permeability, particularly for the transport of large metabolic hormones such as adiponectin.
Methods
We used 2-dimensional monolayers of cultured human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) as well as 3-dimensional microvascular networks to measure transendothelial flux.
Results
Iron supplementation reduced transendothelial electric resistance (TEER). Flux analysis indicated that under control conditions permeability of 70 kDa dextran and oligomeric forms of adiponectin were restricted in comparison with a 3 kDa dextran, however upon iron treatment permeability of the larger molecules was increased. The increased permeability and size-dependent trans-endothelial movement in response to iron was also observed in 3-dimensional microvascular networks. Mechanistically, the alteration in barrier functionality was associated with increased oxidative stress in response to iron since alterations in TEER and permeability were rescued when reactive oxygen species production was attenuated by pre-treatment with the antioxidant N-acetyl cysteine.].
Conclusions
Iron supplementation induced ROS production resulting in increased transendothelial permeability.
General significance
Altogether, this suggests that the oxidative stress associated with iron excess could play an important role in the regulation of endothelial functionality, controlling hormone action in peripheral tissues by regulating the first rate-limiting step controlling hormone access to target tissues.
中文翻译:
在微流控设备上使用二维细胞单层和三维微血管网络显示,铁通过诱导ROS产生而增加跨内皮脂联素通量
背景
铁过量是心血管疾病的危险因素,重要的是要了解铁对血管通透性的影响,特别是对于大代谢激素(如脂连蛋白)的运输。
方法
我们使用培养的人真皮微血管内皮细胞(HDMEC)和人脐静脉静脉内皮细胞(HUVEC)的二维单层膜以及三维微血管网络来测量跨内皮通量。
结果
铁补充降低了跨内皮电阻(TEER)。通量分析表明,在控制条件下,与3kDa葡聚糖相比,70 kDa葡聚糖和脂联素的寡聚形式的通透性受到限制,但是在铁处理后,较大分子的通透性增加。在3维微血管网络中也观察到了对铁的响应的增加的渗透性和尺寸依赖性的跨内皮运动。从机理上讲,屏障功能的改变与铁反应引起的氧化应激增加有关,因为当用抗氧化剂N-乙酰基半胱氨酸预处理减弱了活性氧的产生后,TEER和通透性的改变得以挽救。
结论
铁补充引起ROS产生导致跨内皮通透性增加。
一般意义
总之,这表明与铁过量相关的氧化应激可能在内皮功能的调节中起重要作用,通过调节控制激素进入靶组织的第一个限速步骤来控制外周组织中的激素作用。