Atherosclerosis is initiated by vascular endothelial dysfunction, and low-shear stress (LSS) of blood flow is a key factor leading to endothelial dysfunction. Growing evidence suggests that endothelial cell pyroptosis plays an important role in the development of atherosclerosis. Studies have shown that low-shear stress can induce endothelial cell pyroptosis, but the exact mechanism remains unclear. Our experiments demonstrated that low-shear stress induced endothelial cell pyroptosis and the phosphorylation of IκB kinase ε (IKKε). IKKε knockdown not only significantly attenuated atherosclerosis lesions of aortic arch areas in ApoE^−/− mice fed with high cholesterol diets, but also markedly reduced endothelial cell pyroptosis and NLRP3 expression triggered by low-shear stress. Further mechanism studies showed that IKKε promoted the expression of NLRP3 via activating signal transducer and activator of transcription 1 (STAT1) and the subsequent binding of STAT1 to NLRP3 promoter region. These results suggest that low-shear stress plays a pro-atherosclerotic role by promoting endothelial cell pyroptosis through the IKKε/STAT1/NLRP3 pathway, which provides new insights into the formation of atherosclerosis.

动脉粥样硬化是由血管内皮功能障碍引发的，血流低剪切应力（LSS）是导致内皮功能障碍的关键因素。越来越多的证据表明内皮细胞焦亡在动脉粥样硬化的发展中起着重要作用。研究表明低剪切应力可诱发内皮细胞焦亡，但具体机制尚不清楚。我们的实验表明，低剪切应力诱导内皮细胞焦亡和 IκB 激酶 ε (IKKε) 磷酸化。 IKKε 敲低不仅显着减轻了高胆固醇饮食喂养的ApoE ^−/−小鼠主动脉弓区域的动脉粥样硬化病变，而且还显着减少了低剪切应力引发的内皮细胞焦亡和 NLRP3 表达。进一步的机制研究表明，IKKε通过激活信号转导子和转录激活子1（STAT1）以及随后STAT1与NLRP3启动子区的结合来促进NLRP3的表达。这些结果表明，低剪切应力通过IKKε/STAT1/NLRP3途径促进内皮细胞焦亡，从而发挥促动脉粥样硬化的作用，这为动脉粥样硬化的形成提供了新的见解。