Atherosclerosis has become a major cause of mortality for several years, however the underlying mechanism of this disorder is still complicated. Endothelial dysfunction is a hallmark in the beginning of atherosclerosis. Lipopolysaccharides (LPS) is an important risk factor contributing to endothelial dysfunction. This study demonstrates that Halofuginone, an anti-malarial drug, possesses protective effects on human umbilical vein endothelial cells (HUVECs) against LPS-induced endothelial dysfunction. Through this study, we demonstrate that Halofuginone ameliorates LPS-induced attachment of THP-1 cells to HUVECs by inhibiting the expressions of adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Halofuginone also suppresses the production of pro-inflammatory cytokines, including tumor necrosis factor α.

(TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6). Furthermore, Halofuginone reduces the overproduction of reactive oxygen species (ROS) by regulating the expression of NADPH oxidase 2 (NOX-2). Mechanistically, we find the protective effects of Halofuginone depend on the expression of Kruppel-like factor 2 (KLF2), which is mediated by extracellular regulated protein kinases 5 (ERK5). Totally, our findings demonstrate that Halofuginone possesses a protective function in endothelial cells, indicating a therapeutic potential to modulate endothelial dysfunction in atherosclerosis.

几年来，动脉粥样硬化已经成为导致死亡的主要原因，但是这种疾病的潜在机制仍然很复杂。内皮功能障碍是动脉粥样硬化开始的标志。脂多糖（LPS）是导致内皮功能障碍的重要危险因素。这项研究表明，抗疟药Halofuginone对人脐静脉内皮细胞（HUVEC）具有抵抗LPS诱导的内皮功能障碍的保护作用。通过这项研究，我们证明了卤丁酮可以通过抑制包括血管细胞粘附分子1（VCAM-1）和E-选择素在内的粘附分子的表达来改善LPS诱导的THP-1细胞与HUVEC的附着。halofuginone还抑制促炎性细胞因子的产生，包括肿瘤坏死因子α。

（TNF-α），白介素-1β（IL-1β）和白介素6（IL-6）。此外，卤丁酮可以通过调节NADPH氧化酶2（NOX-2）的表达来减少活性氧（ROS）的过量产生。从机理上讲，我们发现卤氟丁酮的保护作用取决于细胞外调节蛋白激酶5（ERK5）介导的Kruppel样因子2（KLF2）的表达。总的来说，我们的研究结果表明卤丁酮具有在内皮细胞中的保护功能，表明在动脉粥样硬化中调节内皮功能障碍的治疗潜力。