Endothelial cell injury is confirmed to be the initial step in the atherosclerosis (AS) process. Here, we tried to elucidate the role of liver kinase B1 (LKB1) and adenosine phosphate protein kinase (AMPK) in modulating vascular endothelial cells (VECs) in AS. High-fat feed (HFD)-induced AS rat models were prepared and treated with AMPK activator A-769662 alone or combined with chloroquine. An analysis of VEC injury, inflammation response, and autophagy followed it. The M1 linear ubiquitination of LKB1 was assessed by co-immunoprecipitation. The interaction between LKB1 and AMPK was analyzed. Primary aortic VECs were isolated and induced by LPS to verify the effects of LKB1 and AMPK on VEC injury in AS. Activation of AMPK reduced the VEC injury and inflammatory response of VECs and promoted autophagy caused by AS. LKB1 could regulate the activation of AMPK in AS. M1 linear ubiquitination enhanced LKB1 activity and increased AMPK activation to protect against VEC injury in AS, which was validated by in vitro experiments. Our current study highlighted that M1 linear ubiquitination of LKB1 may induce the activation of LKB1 to activate AMPK, which inhibited VEC injury in AS.

内皮细胞损伤被证实是动脉粥样硬化（AS）过程的第一步。在这里，我们试图阐明肝激酶 B1 (LKB1) 和磷酸腺苷蛋白激酶 (AMPK) 在调节 AS 血管内皮细胞 (VEC) 中的作用。制备高脂饲料 (HFD) 诱导的 AS 大鼠模型，并单独用 AMPK 激活剂 A-769662 或与氯喹联合治疗。随后对 VEC 损伤、炎症反应和自噬进行了分析。通过免疫共沉淀评估 LKB1 的 M1 线性泛素化。分析了 LKB1 和 AMPK 之间的相互作用。分离并用 LPS 诱导原发性主动脉 VEC，以验证 LKB1 和 AMPK 对 AS 中 VEC 损伤的影响。AMPK的激活减轻了VEC的损伤和VEC的炎症反应，促进了AS引起的自噬。LKB1可以调节AS中AMPK的激活。M1 线性泛素化增强了 LKB1 活性并增加了 AMPK 激活，以防止 AS 中的 VEC 损伤，这已通过体外实验得到验证。我们目前的研究强调，LKB1 的 M1 线性泛素化可能诱导 LKB1 激活 AMPK，从而抑制 AS 中的 VEC 损伤。