BTK Promotes Atherosclerosis by Regulating Oxidative Stress, Mitochondrial Injury, and ER Stress of Macrophages
Autor: | Shi Liang, Lisui Zhang, Zhi-Teng Chen, Ya-Jing Wang, Junxiong Qiu, Zhuzhi Wen, Yuan Fu, Feng Wei, Diefei Liang, Ling Li |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Aging Article Subject Inflammation 030204 cardiovascular system & hematology medicine.disease_cause Biochemistry Mice 03 medical and health sciences 0302 clinical medicine immune system diseases In vivo hemic and lymphatic diseases Agammaglobulinaemia Tyrosine Kinase medicine Animals Humans Bruton's tyrosine kinase Gene knockdown QH573-671 biology Chemistry Macrophages Cell Biology General Medicine Middle Aged Atherosclerosis Endoplasmic Reticulum Stress Cell biology Oxidative Stress 030104 developmental biology Unfolded protein response biology.protein Female medicine.symptom Cytology Tyrosine kinase Oxidative stress Research Article Lipoprotein |
Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2021 (2021) |
ISSN: | 1942-0994 1942-0900 |
Popis: | Atherosclerosis (AS) is a chronic metabolic disease in arterial walls, characterized by lipid deposition and persistent aseptic inflammation. AS is regarded as the basis of a variety of cardiovascular and cerebrovascular diseases. It is widely acknowledged that macrophages would become foam cells after internalizing lipoprotein particles, which is an initial factor in atherogenesis. Here, we showed the influences of Bruton’s tyrosine kinase (BTK) in macrophage-mediated AS and how BTK regulates the inflammatory responses of macrophages in AS. Our bioinformatic results suggested that BTK was a potential hub gene, which is closely related to oxidative stress, ER stress, and inflammation in macrophage-induced AS. Moreover, we found that BTK knockdown could restrain ox-LDL-induced NK-κB signaling activation in macrophages and repressed M1 polarization. The mechanistic studies revealed that oxidative stress, mitochondrial injury, and ER stress in macrophages were also suppressed by BTK knockdown. Furthermore, we found that sh-BTK adenovirus injection could alleviate the severity of AS in ApoE-/- mice induced by a high-fat diet in vivo. Our study suggested that BTK promoted ox-LDL-induced ER stress, oxidative stress, and inflammatory responses in macrophages, and it may be a potential therapeutic target in AS. |
Databáze: | OpenAIRE |
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