Sestrin2 increases in aortas and plasma from aortic dissection patients and alleviates angiotensin II-induced smooth muscle cell apoptosis via the Nrf2 pathway
Sestrin2 increases in aortas and plasma from aortic dissection patients and alleviates angiotensin II-induced smooth muscle cell apoptosis via the Nrf2 pathway
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Sestrin2 增加主动脉夹层患者的主动脉和血浆，并通过 Nrf2 途径减轻血管紧张素 II 诱导的平滑肌细胞凋亡
DOI：
10.1016/j.lfs.2018.12.043
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Liu Hongtao
中科院分区：
文献类型：
--
作者：
Xiao Ting;Zhang Le;Huang Ying;Shi Ying;Wang Jing;Ji Qingwei;Ye Jing;Lin Yingzhong;Liu Hongtao
背景研究表明氧化应激与主动脉夹层（aortic dissection，AD）密切相关. Sestrin 2（Sesn 2）是一种重要的抗氧化蛋白，本研究旨在探讨Sesn 2是否参与AD及其可能的机制。方法检测Sesn 2在AD患者和正常供体主动脉中的表达。此外，从AD患者和非AD（NAD）患者收集血液样品，并测量血浆Sesn 2水平。此外，Sesn 2对血管紧张素（Ang）II诱导的平滑肌细胞（SMC）凋亡的影响进行了调查在vitro.ResultsCompared from the arrhythmia from normal donors，arrhythmia from AD patients had significantly increased Sesn 2. Sesn 2主要由巨噬细胞分泌，少量由CD4+ T淋巴细胞分泌，但不由SMC分泌。与NAD患者相比，AD患者的血浆Sesn2水平也增加。Sesn 2水平与超氧化物歧化酶（SOD）水平呈负相关，但与丙二醛（MDA）水平呈正相关。在巨噬细胞和SMC共培养中，Sesn2在巨噬细胞中的过表达可显著降低Ang II诱导的SMC凋亡，这种作用可被Nrf2沉默逆转。Sesn2可能通过Nrf2途径减轻Ang II诱导的SMC凋亡，参与AD的发生。Sesn 2可能成为AD治疗和预防的新靶点。
BackgroundPrevious studies have demonstrated that oxidative stress is closely related to aortic dissection (AD). Sestrin2 (Sesn2) is an important antioxidant protein, and this study aimed to investigate whether Sesn2 participates in AD and the possible mechanisms.MethodsSesn2 expression was detected in aortas collected from AD patients and normal donors. In addition, blood samples were collected from AD patients and non-AD (NAD) patients, and the plasma Sesn2 levels were measured. Furthermore, the effects of Sesn2 on angiotensin (Ang) II-induced smooth muscle cell (SMC) apoptosis were investigated in vitro.ResultsCompared with the aortas from normal donors, aortas from AD patients had significantly increased Sesn2. Sesn2 was mainly secreted by macrophages, and low levels were secreted by CD4+ T lymphocytes, but not SMCs. Plasma Sesn2 levels were also increased in AD patients compared with NAD patients. Sesn2 levels were negatively corrected with superoxide dismutase (SOD) levels but positively corrected with malondialdehyde (MDA) levels in AD patients. In co-cultures of macrophages and SMCs, Sesn2 overexpression in macrophages significantly reduced Ang II-induced SMC apoptosis, and this effect could be reversed by Nrf2 silencing.ConclusionsSesn2 is increased in both aortas and plasma from AD patients. Sesn2 may alleviate Ang II-induced SMC apoptosis and participate in AD via the Nrf2 pathway. Sesn2 may be a new target in the treatment and prevention of AD.