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PTP1B Modulates Carotid Plaque Vulnerability in Atherosclerosis Through Rab5-PDGFRβ-Mediated Endocytosis Disruption and Apoptosis

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Pubmed体系：

收录情况： ◇ SCIE

作者：
Zhang Xiao[1,2] * ; Xu Ran[1,2] * ; Wang Tao[1,2] * ; Li Jiayao[1,2] ; Sun Yixin[3,4] ; Cui Shengyan[1,2] ; Xing Zixuan[5] ; Lyu Xintao[6] ; Yang Ge[7,8] ; Jiao Liqun[1,2,9] ; Li Wenjing[7,8] ;
机构： [1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. [2]China International Neuroscience Institute (China-INI), Beijing, China. [3]First Hospital, Peking University, Beijing, China. [4]Health Science Center, Peking University, Beijing, China. [5]Health Science Center, Xi'an Jiaotong University, Shanxi, China. [6]Capital Medical University, Beijing, China. [7]Laboratory of Computational Biology and Machine Intelligence, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China. [8]School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China. [9]Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
出处：
DOI： 10.1111/cns.70071
ISSN：

关键词： apoptosis atherosclerosis carotid plaque endocytosis disruption PTP1B

摘要：
Protein tyrosine phosphatase 1B (PTP1B) is a protein tyrosine phosphatase and modulates platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR) signaling in vascular smooth muscle cells (VSMCs) via endocytosis. However, the related molecular pathways that participated in the interaction of endo-lysosome and the trafficking of PDGFR are largely unknown. This study aims to determine the subcellular regulating mechanism of PTP1B to the endo-lysosome degradation of PDGFR in atherosclerotic carotid plaques, thereby offering a potential therapeutic target for the stabilization of carotid plaques.The immunohistochemical staining technique was employed to assess the expression levels of both PDGFR-β and Caspase 3 in stable and vulnerable carotid plaques. Tunnel staining was utilized to quantify the apoptosis of carotid plaques. Live-cell imaging was employed to observe endocytic motility, while cell apoptosis was evaluated through Propidium Iodide staining. In an in vivo experiment, ApoE-/- mice were administered a PTP1B inhibitor to investigate the impact of PTP1B on atherosclerosis.The heightened expression of PDGFR-β correlates with apoptosis in patients with vulnerable carotid plaques. At the subcellular level of VSMCs, PDGFR-β plays a pivotal role in sustaining a balanced endocytosis system motility, regulated by the expression of Rab5, a key regulator of endocytic motility. And PTP1B modulates PDGFR-β signaling via Rab5-mediated endocytosis. Additionally, disrupted endocytic motility influences the interplay between endosomes and lysosomes, which is crucial for controlling PDGFR-β trafficking. Elevated PTP1B expression induces cellular apoptosis and impedes migration and proliferation of carotid VSMCs. Ultimately, mice with PTP1B deficiency exhibit a reduction in atherosclerosis.Our results illustrate that PTP1B induces disruption in endocytosis and apoptosis of VSMCs through the Rab5-PDGFRβ pathway, suggesting a potential association with the heightened vulnerability of carotid plaques.© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

基金：
Beijing Hospitals Authority's Ascent Plan (Grand No. DFL20220702), the National Natural Science Foundation of China (Grand No. 82401539), the National Natural Science Foundation of China (Grand No. 82171303), Beijing Nova Program (Grand No. 20230484336), the National Natural Science Foundation of China (Grand No. 82301468), and Beijing Municipal Natural Science Foundation (Grand No. 7244353).
语种：
外文
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PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 2 区 神经科学 2 区 药学
最新[2023]版：
大类 | 1 区 医学
小类 | 2 区 神经科学 2 区 药学
JCR分区：
出版当年[2022]版：
Q1 NEUROSCIENCES Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY Q1 NEUROSCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. [2]China International Neuroscience Institute (China-INI), Beijing, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. [2]China International Neuroscience Institute (China-INI), Beijing, China. [7]Laboratory of Computational Biology and Machine Intelligence, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China. [8]School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China. [9]Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
推荐引用方式(GB/T 7714)：
Zhang Xiao,Xu Ran,Wang Tao,et al.PTP1B Modulates Carotid Plaque Vulnerability in Atherosclerosis Through Rab5-PDGFRβ-Mediated Endocytosis Disruption and Apoptosis[J].CNS Neuroscience & Therapeutics.2024,30(11):e70071.doi:10.1111/cns.70071.
APA：
Zhang Xiao,Xu Ran,Wang Tao,Li Jiayao,Sun Yixin...&Li Wenjing.(2024).PTP1B Modulates Carotid Plaque Vulnerability in Atherosclerosis Through Rab5-PDGFRβ-Mediated Endocytosis Disruption and Apoptosis.CNS Neuroscience & Therapeutics,30,(11)
MLA：
Zhang Xiao,et al."PTP1B Modulates Carotid Plaque Vulnerability in Atherosclerosis Through Rab5-PDGFRβ-Mediated Endocytosis Disruption and Apoptosis".CNS Neuroscience & Therapeutics 30..11(2024):e70071

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