雷帕霉素促进人血管内皮细胞氧化低密度脂蛋白的自噬性降解

ims: Oxidized Low-density lipoprotein (ox-LDL) has a great implication in the initiation of atherosclerosis. Our previous study reported that oxidized low-density lipoprotein (ox-LDL) can activate autophagy in human umbilical vein endothelial cells (HUVECs). Therefore studies designed to elucidate the possible role of rapamycin, an autophagic inducer, in the degradation of ox-LDL by endothelial cells. Main methods: In the present study, we have examined the ox-LDL content determined by flow cytometry. The trafficking of ox-LDL within endothelial cells was analyzed by immunofluorescence microscopy. Western blot was used to detect the protein level of LC3, LAMP1, beclin1 and P62. Key findings: Under these experimental conditions, we found that rapamycin could decrease the ox-LDL content. At 3h point, rapamycin group obviously upregulate Dil-ox-LDL/LC3 and Dil-ox-LDL/LAMP1 co-localization. In addition, at this time point, a significant colocalization of LC3 and LAMP1 occurred in the cells with rapamycin pretreatment. In the presence of rapacymin, autophagic flux was enhanced and P62 level was reduced. Significance: Therefore, these data identify a critical function for rapamycin in ox-LDL metabolism and demonstrate that the activation of autophagic-lysosome pathway by rapamycin may accelerate ox-LDL degradation. This could have important implications on the pathologic process of atherosclerosis. Earlier intervention to increase autophagic function may therefore provide a new approach to prevent ox-LDL accumulation and its associated pathological process.