A major cause of late-life health complications is the cardiovascular disease known as atherosclerosis. The process of atherogenesis is marked by endothelial cell dysfunction, the development of atherogenic lesions, and plaque buildup on the intima of the arterial endothelium. This process is fueled primarily by the adhesion of monocytes to endothelial cells via the actions of the cellular adhesion molecules VCAM-1 and E-selectin. When expressed at their basal levels, these molecules are vital to various cellular processes, but when in a state of overproduction, they drive the progression of atherosclerosis by recruiting monocytes to roll along and adhere to the endothelium. TNF-α is theorized to play a causal role in the development of atherosclerosis, but the exact mechanism remains poorly understood. This cytokine is known to upregulate various factors associated with inflammation and oxidative stress, both of which greatly contribute to endothelial dysfunction and atherogenesis. In the present study, we aimed to elucidate the effect of butyrate on these atherogenic processes. Previously not known to have atheroprotective effects, this natural compound shows promise as a treatment for atherosclerosis. In the present study, we found butyrate to exert various anti-inflammatory and downstream regulatory effects. Namely, butyrate ameliorated the overproduction of adhesion molecules, including VCAM-1 and E-selectin, reduced oxidative stress by reducing the levels of ROS and 4-HNE, and suppressed inflammation via inhibition of MCP-1 and IL-8. Additionally, butyrate rescued the reduced expression of the protective factor KLF2, which was mediated through the ERK5 pathway. Thus, butyrate may serve as a promising treatment against atherosclerosis.

晚年健康并发症的主要原因是心血管疾病，称为动脉粥样硬化。动脉粥样硬化的形成过程以内皮细胞功能障碍，动脉粥样硬化病变的发展以及动脉内皮膜内膜斑的形成为特征。该过程主要由单核细胞通过细胞粘附分子VCAM-1和E-选择素的作用粘附于内皮细胞而加重。当以其基础水平表达时，这些分子对于各种细胞过程至关重要，但是当处于过度生产状态时，它们通过募集单核细胞滚动并粘附于内皮细胞来驱动动脉粥样硬化的发展。从理论上讲，TNF-α在动脉粥样硬化的发展中起着因果作用，但确切的机制仍知之甚少。已知该细胞因子上调与炎症和氧化应激相关的各种因素，这两者都极大地促进了内皮功能障碍和动脉粥样硬化的形成。在本研究中，我们旨在阐明丁酸酯对这些致动脉粥样硬化过程的影响。以前不知道它具有抗动脉粥样硬化的作用，这种天然化合物显示出有望作为动脉粥样硬化的治疗方法。在本研究中，我们发现丁酸酯具有多种抗炎和下游调节作用。即，丁酸酯减轻包括VCAM-1和E-选择素在内的粘附分子的过量产生，通过降低ROS和4-HNE的水平来降低氧化应激，并通过抑制MCP-1和IL-8来抑制炎症。此外，丁酸盐还挽救了保护因子KLF2的减少表达，是通过ERK5途径介导的。因此，丁酸盐可作为抗动脉粥样硬化的有前途的治疗方法。