Sirt6 stabilizes atherosclerosis plaques by promoting macrophage autophagy and reducing contact with endothelial cells
| Autor: | Chuang Sun, Dongdong Sun, Tingting Wang, Haichang Wang, Congye Li, Lang Hu, Erhe Gao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
SIRT6 Mice Knockout ApoE Vascular Cell Adhesion Molecule-1 Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Autophagy Animals Sirtuins Molecular Biology 030304 developmental biology Foam cell Inflammation 0303 health sciences Chemistry Macrophages Vascular biology Endothelial Cells Cell Biology Atherosclerosis Intercellular Adhesion Molecule-1 Receptor TIE-2 Plaque Atherosclerotic Cell biology Lipoproteins LDL P-Selectin RAW 264.7 Cells 030220 oncology & carcinogenesis Disease Progression Foam Cells |
| Zdroj: | Biochemistry and Cell Biology. 98:120-129 |
| ISSN: | 1208-6002 0829-8211 |
| DOI: | 10.1139/bcb-2019-0057 |
| Popis: | Sirt6 has been reported to play a protective role in macrophage foam cell formation, but whether Sirt6 controls atherosclerosis plaque stability and whether it can reduce the interaction between endothelial cells and macrophages remains unclear. The aim of this study was to investigate the effect of Sirt6 on atherosclerosis plaque stability and the underlying mechanisms. We used Tie2-Cre transgenic mice as a Cre-lox tool to delete Sirt6 floxed sequences in endothelial cells during adulthood to establish Sirt6−/− mice. ApoE−/−:Sirt6−/− and ApoE−/−:Sirt6Tg mice were used in our investigation. After a 16 week high-fat diet, the mice developed markedly atherosclerotic plaques. Sirt6 knockout exacerbated atherosclerotic plaque progression in both size and stability. In vitro, murine macrophage RAW264.7 cells were treated with ox-low density lipoproteins for 24 h to simulate atherosclerosis. Furthermore, Sirt6 overexpression remarkably increased autophagic flux in macrophages and inhibited macrophage apoptosis. Moreover, Sirt6 overexpression inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and platelet selectin (P-selectin), leading to reduced infiltration of macrophages and foam cells. In conclusion, our study indicates a new mechanism-based strategy to therapeutically stimulate atherosclerosis plaque stability. |
| Databáze: | OpenAIRE |
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