炎症
氧化应激
活性氧
化学
脐静脉
细胞生物学
载脂蛋白E
泡沫电池
药理学
脂蛋白
免疫学
生物化学
胆固醇
医学
生物
病理
疾病
体外
作者
Wanling Liu,Yihong Zhang,Gen Wei,Minxuan Zhang,Tong Li,Quanyi Liu,Zijun Zhou,Ying Du,Hui Wei
标识
DOI:10.1002/anie.202304465
摘要
Abstract Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase‐ and glutathione peroxidase‐like activities, named MSe 1 , is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe 1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low‐density lipoprotein. After intravenous administration, the MSe 1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E‐deficient (ApoE −/− ) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.
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