Mouse macrophage specific knockout of SIRT1 influences macrophage polarization and promotes angiotensin II-induced abdominal aortic aneurysm formation

State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, No.5 Dong Dan San Tiao, Beijing 100005, China

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Corresponding author: E-mail address: chenhouzao@ibms.cams.cn (Hou-Zao Chen); E-mail address: liudp@pumc.edu.cn (De-Pei Liu)

These authors contributed equally to this work.

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Abstract: 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 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 ofSIRT1 influences macrophage polarization and accelerates Ang II-induced AAA formation.
- SIRT1 /
- Inflammation /
- Macrophage polarization /
- Abdominal aortic aneurysm
These authors contributed equally to this work.
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doi: 10.1016/j.jgg.2018.01.002

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Mouse macrophage specific knockout of SIRT1 influences macrophage polarization and promotes angiotensin II-induced abdominal aortic aneurysm formation

Corresponding author: E-mail address: chenhouzao@ibms.cams.cn (Hou-Zao Chen); E-mail address: liudp@pumc.edu.cn (De-Pei Liu)

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doi: 10.1016/j.jgg.2018.01.002

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Mouse macrophage specific knockout of SIRT1 influences macrophage polarization and promotes angiotensin II-induced abdominal aortic aneurysm formation

Corresponding author: E-mail address: chenhouzao@ibms.cams.cn (Hou-Zao Chen); E-mail address: liudp@pumc.edu.cn (De-Pei Liu)

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