Jing Xu
Yue Liu
Tingting Wang
Jianfei Pei
Liqin Cheng
Delong Hao
Xiang Zhao
Hou-Zao Chen
De-Pei Liu
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
More InformationCorresponding author: E-mail address: chenhouzao@ibms.cams.cn (Hou-Zao Chen);E-mail address: liudp@pumc.edu.cn (De-Pei Liu)
Received Date: 2017-08-03
Accepted Date:2018-01-11
Rev Recd Date:2018-01-06
Available Online: 2018-01-17 Publish Date:2018-01-20
Abstract
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.Keywords: SIRT1,
Inflammation,
Macrophage polarization,
Abdominal aortic aneurysm
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