The inflammatory response and oxidative stress play key roles in the formation and development of atherosclerosis. Bazedoxifene is a new IL6/GP130 inhibitor recommended by the FDA for clinical use as a selective estrogen receptor modulator. However, its role in cardiovascular diseases has been poorly studied. In our study, we explored the mechanism of bazedoxifene’s protective effect against inflammatory injury of vascular endothelial cells (VECs) stimulated by TNF-α. Various methods were used to verify the effect of bazedoxifene on VECs, including a cell viability assay, a wound healing assay, immunofluorescence staining, and western blotting. Our results showed that TNF-α could induce inflammatory damage to VECs, which manifested as upregulated expression of CD40, increased production of ROS, enhanced adhesion of THP-1 cells to VECs, and impaired viability and migration of VECs, while bazedoxifene could significantly reduce the endothelial damage caused by TNF-α. In addition, we found that an siRNA targeting CD40 dramatically alleviated the VEC damage induced by TNF-α. Therefore, we explored the potential relationship between bazedoxifene and CD40. Our data suggest that bazedoxifene has a protective effect against VEC damage induced by TNF-α and that its underlying mechanism may be related to the regulation of CD40.

中文翻译：

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Bazedoxifene通过靶向CD40发挥抗内皮细胞炎性损伤的保护作用

炎症反应和氧化应激在动脉粥样硬化的形成和发展中起关键作用。Bazedoxifene是FDA推荐用于临床的选择性雌激素受体调节剂，是一种新型的IL6 / GP130抑制剂。但是，其在心血管疾病中的作用研究很少。在我们的研究中，我们探讨了巴多昔芬对TNF- α刺激的血管内皮细胞（VECs）炎症损伤的保护作用机制。使用了多种方法来验证巴多昔芬对VEC的作用，包括细胞活力测定，伤口愈合测定，免疫荧光染色和蛋白质印迹。我们的结果表明，TNF- α可以诱导对VEC的炎性损伤，表现为CD40表达上调，ROS产生增加，THP-1细胞与VEC的粘附增强，VEC的活力和迁移受损，而巴多昔芬可以显着减少TNF-α引起的内皮损伤α。另外，我们发现靶向CD40的siRNA显着减轻了由TNF- α诱导的VEC损伤。因此，我们探讨了巴多昔芬与CD40之间的潜在关系。我们的数据表明，巴多昔芬对TNF- α引起的VEC损伤具有保护作用，其潜在机制可能与CD40的调节有关。