Introduction

Atherosclerosis is characterized by endothelial cell dysfunction followed by lesion formation, arterial stenosis, potentially arterial occlusion, and severe outcomes. Novel treatments to slow or prevent the progression of the disease are of considerable clinical value. In the present study, we investigated the potential anti-atherosclerotic effects of the natural product juglanin in oscillatory shear stress (OSS) exposed endothelial cells.

Methods

Human aortic endothelial cells (HAECs) were exposed to OSS generated by a micro fluidal Teflon cone at 1 Hz frequency cycles (±5 dyn/cm²) in the presence or absence of 2.5 and 5 μM juglanin for 24 h. The expression levels of inflammatory factors and vascular adhesion molecules were evaluated using qRT-PCR, Western Blot, and ELISA. DHE assay was used to detect the production of ROS. The monocytic THP-1 cells were labeled with calcein-AM and incubated with HAECs for adhesion assay.

Results

Juglanin reduces OSS-induced oxidative stress by reducing the production of ROS through downregulation of NOX-2 and rescuing OSS-induced reduced expression of eNOS. Juglanin also inhibits the inflammatory response by suppressing OSS-induced expressions of IL-1β, MCP-1, and HMGB1. Using THP-1 monocytes, we show that juglanin reduces the attachment of monocytes to endothelial cells by inhibiting the expression of VCAM-1 and E-selectin. Moreover, Juglanin rescues OSS-reduced expression of atheroprotective transcriptional factor KLF2.

Conclusions

Our findings indicate that juglanin protects against various atheroprone OSS-induced endothelial dysfunction. Juglanin has potential implication as a candidate for vascular intervention of atherosclerosis.

中文翻译：

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Juglanin抑制振荡剪切应力引起的内皮功能障碍：对动脉粥样硬化的影响

介绍

动脉粥样硬化的特征是内皮细胞功能障碍，继之以病变形成，动脉狭窄，潜在的动脉闭塞和严重预后。减慢或预防疾病进展的新疗法具有可观的临床价值。在本研究中，我们研究了天然产物胡桃宁在振荡剪切应力（OSS）暴露的内皮细胞中的潜在抗动脉粥样硬化作用。

方法

在存在或不存在2.5μM和5μM胶凝素的情况下，将人类主动脉内皮细胞（HAEC）暴露于微流体特氟隆锥以1 Hz频率周期（±5 dyn / cm ²）生成的OSS暴露24 h。使用qRT-PCR，Western Blot和ELISA评估炎症因子和血管黏附分子的表达水平。用DHE测定法检测ROS的产生。用钙黄绿素-AM标记单核细胞THP-1细胞，并与HAEC一起孵育以进行粘附测定。

结果

Juglanin通过下调NOX-2减少ROS的产生并拯救OSS诱导的eNOS表达减少，从而降低OSS诱导的氧化应激。Juglanin还通过抑制OSS诱导的IL-1β，MCP-1和HMGB1的表达来抑制炎症反应。使用THP-1单核细胞，我们显示了胡桃苷通过抑制VCAM-1和E-选择素的表达减少了单核细胞对内皮细胞的附着。此外，Juglanin可挽救OSS降低的抗动脉粥样硬化转录因子KLF2的表达。

结论

我们的发现表明，胡桃宁可防止多种由动脉粥样硬化引起的OSS诱导的内皮功能障碍。胡桃宁可能作为动脉粥样硬化血管介入治疗的候选药物。