Endothelial dysfunction (ED) is a critical and initiating factor in the genesis of diabetic vascular complications whose occurrence and development is closely related to the complex intravascular microenvironment. However, currently, there is no dynamic model simulating the diabetic vascular endothelial microenvironment that can be used to investigate the mechanism underlying multifactor-induced ED. Here, we developed an integrated microfluidic chip as a new methodological platform to study vascular ED. Selenoprotein S (SELENOS) was found to be involved in the defense against oxidative stress-induced vascular endothelial injury in our previous studies. However, the regulatory signaling pathway underlying this process has not been described. With this chip, we demonstrated that multifactor-induced oxidative stress injury in human aortic endothelial cells (HAECs) has a synergistic effects and upregulates SELENOS expression. Subsequently, SELENOS was found to protect HAECs against multifactor-induced oxidative stress injury by regulating the PKCα/PI3K/Akt/eNOS pathway in the diabetic vascular endothelial microenvironment. Based on these data, our diabetic vascular chip provides a promising tool for studying vascular endothelial function, and SELENOS may be a novel target for prevention and treatment of diabetic macrovascular complications.

中文翻译：

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硒蛋白S减弱糖尿病性血管芯片中的内皮功能障碍。

内皮功能障碍（ED）是糖尿病血管并发症发生的关键和起始因素，其发生和发展与复杂的血管内微环境密切相关。但是，目前尚没有可用于研究糖尿病血管内皮微环境的动态模型来研究多因素诱导的ED的机制。在这里，我们开发了一种集成的微流控芯片作为研究血管性ED的新方法平台。在我们以前的研究中，发现硒蛋白S（SELENOS）参与了抗氧化应激诱导的血管内皮损伤的防御。但是，尚未描述该过程的调控信号通路。有了这个芯片，我们证明了在人的主动脉内皮细胞（HAECs）中多因素诱导的氧化应激损伤具有协同效应，并上调了SELENOS的表达。随后，发现SELENOS可通过调节糖尿病血管内皮微环境中的PKCα/ PI3K / Akt / eNOS途径来保护HAEC免受多因素诱导的氧化应激损伤。基于这些数据，我们的糖尿病血管芯片为研究血管内皮功能提供了有前途的工具，并且SELENOS可能是预防和治疗糖尿病大血管并发症的新靶标。发现SELENOS通过调节糖尿病血管内皮微环境中的PKCα/ PI3K / Akt / eNOS途径来保护HAEC免受多因素诱导的氧化应激损伤。基于这些数据，我们的糖尿病血管芯片为研究血管内皮功能提供了有前途的工具，并且SELENOS可能是预防和治疗糖尿病大血管并发症的新靶标。发现SELENOS通过调节糖尿病血管内皮微环境中的PKCα/ PI3K / Akt / eNOS途径来保护HAEC免受多因素诱导的氧化应激损伤。基于这些数据，我们的糖尿病血管芯片为研究血管内皮功能提供了有前途的工具，并且SELENOS可能是预防和治疗糖尿病大血管并发症的新靶标。