eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque
文献类型:期刊论文
作者 | Luo, Jichang1,2; Zhang, Xiao1,2; Li, Wenjing3,4; Wang, Tao1,2![]() ![]() |
刊名 | HELIYON
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出版日期 | 2024-03-15 |
卷号 | 10期号:5页码:14 |
关键词 | Carotid artery atherosclerosis Primary vascular smooth muscle cells Organelles Plaque vulnerability Translation initiation factor 2 alpha |
DOI | 10.1016/j.heliyon.2024.e26904 |
通讯作者 | Yang, Ge(ge.yang@ia.ac.cn) ; Xu, Ran(xrqssq@126.com) ; Jiao, Liqun(liqunjiao@sina.cn) |
英文摘要 | Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2 alpha-dependent manner. Furthermore, the effects of eIF2 alpha on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. |
WOS关键词 | INDUCTION ; STENOSIS ; ER |
资助项目 | Beijing Science and Technologic Project[Z201100005520020] ; National Natural Science Foun-dation of China[82171303] ; Beijing Municipal Science &Technology Commission[5202022] |
WOS研究方向 | Science & Technology - Other Topics |
语种 | 英语 |
WOS记录号 | WOS:001195970500001 |
出版者 | CELL PRESS |
资助机构 | Beijing Science and Technologic Project ; National Natural Science Foun-dation of China ; Beijing Municipal Science &Technology Commission |
源URL | [http://ir.ia.ac.cn/handle/173211/58076] ![]() |
专题 | 模式识别国家重点实验室_计算生物学与机器智能 |
通讯作者 | Yang, Ge; Xu, Ran; Jiao, Liqun |
作者单位 | 1.Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing, Peoples R China 2.China Int Neurosci Inst China INI, Beijing, Peoples R China 3.Chinese Acad Sci, Inst Automat, Lab Computat Biol & Machine Intelligence, Natl Lab Pattern Recognit, Beijing, Peoples R China 4.Univ Chinese Acad Sci, Sch Artificial Intelligence, Beijing, Peoples R China 5.Capital Med Univ, Inst Cerebrovascular Dis Res, Xuanwu Hosp, Beijing, Peoples R China 6.Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing, Peoples R China 7.Capital Med Univ, Xuanwu Hosp, Dept Intervent Radiol, Beijing, Peoples R China |
推荐引用方式 GB/T 7714 | Luo, Jichang,Zhang, Xiao,Li, Wenjing,et al. eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque[J]. HELIYON,2024,10(5):14. |
APA | Luo, Jichang.,Zhang, Xiao.,Li, Wenjing.,Wang, Tao.,Cui, Shengyan.,...&Jiao, Liqun.(2024).eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque.HELIYON,10(5),14. |
MLA | Luo, Jichang,et al."eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque".HELIYON 10.5(2024):14. |
入库方式: OAI收割
来源:自动化研究所
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