Mouse macrophage specific knockout of SIRT1 influences macrophage polarization and promotes angiotensin II-induced abdominal aortic aneurysm formation
| Autor: | Yue Liu, Jing Xu, Xiang Zhao, Tingting Wang, Jian-Fei Pei, De-Pei Liu, De-Long Hao, Hou-Zao Chen, Zhu-Qin Zhang, Li-Qin Cheng |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Macrophage polarization Nitric Oxide Synthase Type II Receptors Cell Surface Inflammation macromolecular substances Biology environment and public health Mice 03 medical and health sciences Sirtuin 1 Internal medicine Genetics medicine Animals Humans Macrophage Lectins C-Type Molecular Biology Aorta Mice Knockout Arginase Angiotensin II Macrophages Cell Polarity Nitric oxide synthase Disease Models Animal enzymes and coenzymes (carbohydrates) Mannose-Binding Lectins 030104 developmental biology Endocrinology Knockout mouse cardiovascular system biology.protein medicine.symptom Mannose Receptor hormones hormone substitutes and hormone antagonists Mannose receptor Aortic Aneurysm Abdominal Signal Transduction |
| Zdroj: | Journal of Genetics and Genomics. 45:25-32 |
| ISSN: | 1673-8527 |
| DOI: | 10.1016/j.jgg.2018.01.002 |
| Popis: | Abdominal aortic aneurysm (AAA) is a vascular degenerative disease. Macrophage polarization and the balance between classically activated macrophages (M1) and alternatively activated macrophages (M2) are crucial for AAA pathogenesis. The present study aims to investigate the roles of macrophage SIRT1 in AAA formation and macrophage polarization. We found that in mouse peritoneal macrophages, SIRT1 expression was decreased after M1 stimulation, but was enhanced after M2 stimulation. Results from SIRT1flox/flox mice and macrophage specific SIRT1 knockout mice with treatment of angiotensin II (Ang II) for 4 weeks showed that macrophage specific deficiency of SIRT1 increased the incidence of AAA and exacerbated the severity, including more severe aneurysm types, enlarged diameter of the aneurysm and increased degradation of elastin. In mouse aortas, SIRT1 deficiency increased the pro-inflammatory M1 molecule inducible nitric oxide synthase (iNOS), and decreased M2 molecules such as arginase 1 (Arg1) and mannose receptor (MR). Furthermore, in peritoneal macrophages, SIRT1 deficiency increased the expression of M1 inflammatory molecules, but decreased the expression of M2 molecules. Overexpression of SIRT1 had the opposite effects. Thus, macrophage specific knockout of SIRT1 influences macrophage polarization and accelerates Ang II-induced AAA formation. |
| Databáze: | OpenAIRE |
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