Icariin alleviates ferroptosis‐related atherosclerosis by promoting autophagy in xo‐LDL‐induced vascular endothelial cell injury and atherosclerotic mice

• DOI: 10.1002/ptr.7854
• Publication Date: 2023-06-24T06:17:54Z
• Authors: Xindong Wang; Meng Zhang; Chenhan Mao; Chengbo Zhang; Wenqi Ma; Jiahui Tang; Dongyang Xiang; Xiaoxia Qi
• Keywords: TFEB; Icariin

Abstract Vascular endothelial cells (VECs) are located between the blood plasma and vascular tissue, ferroptosis (iron‐dependent programmed cell death) of VECs can lead to a range cardiovascular diseases. Icariin is main active ingredient Epimedium brevicornum Maxim., which improve dysfunction. In present study, protective effects icariin on oxidised low‐density lipoprotein (ox‐LDL)‐treated high‐fat diet‐fed Apolipoprotein E‐deficient mice were investigated. Inflammatory fibrosis in tissues inflammatory factors serum supernatants detected, mitochondrial membrane potential expression levels ferroptosis‐associated proteins also detected. The results revealed that reduced atherosclerotic plaque area collagen fibres aortic sinus increased viability potential, whereas it reactive oxygen species VECs. nucleation transcription factor EB (TFEB) subsequent autophagy negatively associated with cells, more prominent autophagy, lower ferroptosis. Furthermore, by co‐treating two inhibitors, Bafilomycin A1 (blocking autophagosome lysosome fusion) 3‐methyladenine formation), respectively, promoting found be mediated through process autophagosome–lysosome fusion. vivo experiments, ferroptosis, alleviated lesions rate TFEB nucleation. Additionally, was ARG304, THR308 GLN311 optimal binding sites for interaction TFEB. Taken together, these suggest fusion autophagosomes lysosomes promoted icarrin enhances thus reduces Therefore, may candidate prevention and, thus, treatment