中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
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; Cui, Shengyan1,2; Li, Tianhua1,2; Wang, Yilin5,6; Xu, Wenlong1,2; Ma, Yan1,2; Yang, Bin1,2
刊名HELIYON
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
DOI10.1016/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.

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