التفاصيل البيبلوغرافية
| العنوان: |
Sirt4 deficiency promotes the development of atherosclerosis by activating the NF-κB/IκB/CXCL2/3 pathway. |
| المؤلفون: |
Chang, Shuting1,2 (AUTHOR), Zhang, Guanzhao2 (AUTHOR), Li, Lanlan3 (AUTHOR), Li, Haiying4 (AUTHOR), Jin, Xiaodong5 (AUTHOR), Wang, Yunshan2,6 (AUTHOR) wangyunshan135@126.com, Li, Bo2 (AUTHOR) libosubmit@163.com |
| المصدر: |
Atherosclerosis (00219150). May2023, Vol. 373, p29-37. 9p. |
| مصطلحات موضوعية: |
*ATHEROSCLEROSIS, *STAINS & staining (Microscopy), *PERITONEAL macrophages, *ENZYME-linked immunosorbent assay, *ORAL hygiene products, *HEMATOXYLIN & eosin staining, *POLYMERASE chain reaction, *LINSEED oil |
| مستخلص: |
As a member of mitochondrial sirtuins, Sirt4 plays a vital role in cellular metabolism and intracellular signal transduction; however, its effect on atherosclerosis is unclear. This study aimed to explore the effect of Sirt4 on atherosclerosis and its underlying mechanism. In vivo , Apoe −/− and Apoe −/− /Sirt4 −/− mice were fed a high-fat diet to induce atherosclerosis. In vitro , peritoneal macrophages from two mouse types were extracted and treated with oxidized low-density lipoprotein to establish a cell model, THP-1 cells were used to observe the effect of Sirt4 on the adhesion ability of monocytes. The growth and composition of aortic plaques in two mouse types were analyzed by H&E staining, Oil Red O staining, Dil oxidized low-density lipoprotein, immunohistochemistry, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Transcriptome analysis and Western blotting were performed to explore the specific mechanism. Sirt4 deficiency aggravated atherosclerosis in mice. In vivo , aortic plaque size, lipid content, and expression of related inflammatory factors in Apoe −/− /Sirt4 −/− mice were higher than those in the control group, whereas the content of collagen Ⅰ and smooth muscle actin-α was significantly lower. Sirt4-deficient macrophages exhibited stronger lipid phagocytosis in vitro , and the adhesion ability of monocytes increased when Sirt4 expression decreased. Transcriptome analysis showed that the expression of CXCL2 and CXCL3 in Sirt4-deficient peritoneal macrophages increased significantly, which may play a role by activating the NF-κB pathway. In further analysis, the results in vitro and in vivo showed that the expression of VCAM-1 and pro-inflammatory factors, such as IL-6, TNF-α and IL-1β, increased, whereas the expression of anti-inflammatory factor IL-37 decreased in Sirt4-deficient peritoneal macrophages and tissues. After blocking the effect with NK-κB inhibitor BAY11-7082, the inflammatory reaction in sirt4 deficient macrophages was also significantly decreased. This study demonstrates that Sirt4 deficiency promotes the development of atherosclerosis by activating the NF-κB/IκB/CXCL2/3 pathway, suggesting that Sirt4 may exhibit a protective effect in atherosclerosis, which provides a new strategy for clinical prevention and treatment of atherosclerosis. [Display omitted] • Sirt4 deficiency aggravates inflammation and promotes the development of atherosclerosis. • Sirt4 deficiency activates the phosphorylation of NF-κB. • Sirt4 exhibits a protective effect in atherosclerosis. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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