SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells
| العنوان: | SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells |
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| المؤلفون: | Huifeng Pi, Ping Deng, Zhen Wang, Zhengping Yu, Zhou Zhou, Feng Gao, Mengyu Liu |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | John Wiley and Sons Inc., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteomics, Vascular smooth muscle, Myocytes, Smooth Muscle, Muscle, Smooth, Vascular, 03 medical and health sciences, 0302 clinical medicine, Lipid droplet, Autophagy, Humans, lipophagy, Cells, Cultured, Foam cell, oxLDL, TFEB, Chemistry, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Lysosomal proteolysis, Cell Biology, Original Articles, Lipid Droplets, Atherosclerosis, Nuclear translocation, Cell biology, Lipoproteins, LDL, 030104 developmental biology, VSMC foam cell, Gene Expression Regulation, 030220 oncology & carcinogenesis, Molecular Medicine, lipids (amino acids, peptides, and proteins), Original Article, Lysosomes, Biogenesis, SCD1, Stearoyl-CoA Desaturase, Lipoprotein, Foam Cells |
| الوصف: | The formation of fat‐laden foam cells, which contributes to the fatty streaks in the plaques of atheromas, is an important process in atherosclerosis. Vascular smooth muscle cells (VSMCs) are a critical origin of foam cells. However, the mechanisms that underlie VSMC foam cell formation are not yet completely understood. Here, we demonstrated that oxidized low‐density lipoprotein (oxLDL) inhibited lipophagy by suppressing lipid droplet (LD)‐lysosome fusion and increased VSMC foam cell formation. Moreover, although oxLDL treatment inhibited lysosomal biogenesis, it had no significant effect on lysosomal proteolysis and lysosomal pH. Notably, through TMT‐based quantitative proteomic analysis and database searching, 94 differentially expressed proteins were identified, of which 54 were increased and 40 were decreased in the oxLDL group compared with those in the control group. Subsequently, SCD1, a protein of interest, was further investigated. SCD1 levels in the VSMCs were down‐regulated by exposure to oxLDL in a time‐dependent manner and the interaction between SCD1 and LDs was also disrupted by oxLDL. Importantly, SCD1 overexpression enhanced LD‐lysosome fusion, increased lysosomal biogenesis and inhibited VSMC foam cell formation by activating TFEB nuclear translocation and its reporter activity. Modulation of the SCD1/TFEB‐mediated lipophagy machinery may offer novel therapeutic approaches for the treatment of atherosclerosis. |
| اللغة: | English |
| تدمد: | 1582-4934 1582-1838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::879a5159b624f3c2e051ce18877a0f02Test http://europepmc.org/articles/PMC6652860Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....879a5159b624f3c2e051ce18877a0f02 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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