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Methamphetamine induces cardiomyopathy through GATA4/NF-κB/SASP axis-mediated cellular senescence

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机构: [1]Centre of General Practice, The Seventh Affiliated Hospital, Southern Medical University, Foshan 528200, China [2]School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China [3]Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China [4]Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen 518055, China [5]School of Traditional Chinese medicine, Southern Medical University, Guangzhou 510515, China f Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China
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关键词: Methamphetamine (METH) GATA4 Cardiomyopathy Transcriptome Cardiomyocyte senescence

摘要:
With the world pandemic of methamphetamine (METH), METH-associated cardiomyopathy (MAC) has become a widespread epidemic and is also recognized as a cause of heart failure in young people. The mechanism of occurrence and development of MAC is not clear. In this study, firstly, the animal model was evaluated by echocardiography and myocardial pathological staining. The results revealed that the animal model exhibited cardiac injury consistent with clinical alterations of MAC, and the mice developed cardiac hypertrophy and fibrosis remodeling, which led to systolic dysfunction and left ventricular ejection fraction (%LVEF) < 40%. The expression of cellular senescence marker proteins (p16 and p21) and senescence-associated secretory phenotype (SASP) was significantly increased in mouse myocardial tissue. Secondly, mRNA sequencing analysis of cardiac tissues revealed the key molecule GATA4, and Western blot, qPCR and immunofluorescence results showed that the expression level of GATA4 was significantly increased after METH exposure. Finally, knockdown of GATA4 expression in H9C2 cells in vitro significantly attenuated METH-induced cardiomyocyte senescence. Consequently, METH causes cardiomyopathy through cellular senescence mediated by the GATA4/NF-κB/SASP axis, which is a feasible target for the treatment of MAC.Copyright © 2023. Published by Elsevier Inc.

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出版当年[2022]版:
大类 | 3 区 医学
小类 | 2 区 毒理学 2 区 药学
最新[2025]版:
大类 | 3 区 医学
小类 | 2 区 毒理学 3 区 药学
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第一作者机构: [1]Centre of General Practice, The Seventh Affiliated Hospital, Southern Medical University, Foshan 528200, China
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通讯机构: [1]Centre of General Practice, The Seventh Affiliated Hospital, Southern Medical University, Foshan 528200, China [2]School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China [3]Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China [5]School of Traditional Chinese medicine, Southern Medical University, Guangzhou 510515, China f Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China [*1]Centre of General Practice, The Seventh Affiliated Hospital, Southern Medical University, Foshan 528200, China. [*2]School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China
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