SOCS1 prevents graft arteriosclerosis by preserving endothelial cell function.
SOCS1 prevents graft arteriosclerosis by preserving endothelial cell function.
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DOI：
10.1016/j.jacc.2013.08.694
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发表时间：
2014-01-07
影响因子：
24
通讯作者：
Yu, Luyang
中科院分区：
文献类型：
--
作者：
Qin, Lingfeng;Huang, Qunhua;Zhang, Haifeng;Liu, Renjing;Tellides, George;Min, Wang;Yu, Luyang
本研究旨在确定细胞因子信号抑制因子1（SOCS1）在移植物动脉硬化（GA）中的作用。
GA是心脏移植后期移植物衰竭的主要原因，由免疫介导的内皮细胞激活引发，进而导致血管炎症和内膜新生。SOCS1作为细胞因子信号的负调节因子，在内皮细胞（ECs）中高表达，可能阻止内皮细胞的炎症反应和表型激活。
收集患有GA、动脉粥样硬化或无疾病的冠状动脉临床标本进行组织学分析。在GA的主动脉移植模型中使用SOCS1基因敲除小鼠或血管内皮SOCS1转基因小鼠（VESOCS1）。分离小鼠主动脉内皮细胞用于体外实验。
在人类GA和动脉粥样硬化标本中观察到内皮细胞SOCS1显著且特异性减少，这表明SOCS1在维持正常内皮功能中具有重要意义。小鼠体内SOCS1缺失导致基础内皮细胞功能障碍。移植后，SOCS1缺陷的主动脉移植物增强了白细胞募集和内膜新生，而内皮细胞中SOCS1的过表达则减轻了动脉排斥反应。VESOCS1转基因抑制了GA早期内皮细胞黏附分子的诱导表达，这一效应在培养的主动脉内皮细胞中也得到证实。此外，在GA进展过程中，VESOCS1能更好地维持血管功能。从机制上讲，内皮细胞SOCS1通过调节黏附分子PECAM - 1、ICAM - 1和VCAM - 1的基础表达及细胞因子诱导的表达，在炎症细胞浸润过程中抑制白细胞黏附和跨内皮迁移。
SOCS1通过维持内皮细胞功能和减弱细胞因子诱导的血管内皮黏附分子表达来阻止GA进展。
The aim of this study was to determine the role of Suppressor of Cytokine Signaling 1 (SOCS1) in graft arteriosclerosis (GA). GA, the major cause of late cardiac allograft failure, is initiated by immune-mediated endothelial activation resulting in vascular inflammation and consequent neointima formation. SOCS1, a negative regulator of cytokine signaling, is highly expressed in endothelial cells (ECs) and may prevent endothelial inflammatory responses and phenotypic activation. Clinical specimens of coronary arteries with GA, atherosclerosis, or without disease were collected for histological analysis. SOCS1 knockout or vascular endothelial SOCS1 transgenic mice (VESOCS1) were used in an aorta transplant model of GA. Mouse aortic ECs were isolated for in vitro assays. Dramatic but specific reduction of endothelial SOCS1 was observed in human GA and atherosclerosis specimens which suggested the importance of SOCS1 in maintaining normal endothelial function. SOCS1 deletion in mice resulted in basal EC dysfunction. After transplantation, SOCS1-deficient aortic grafts augmented leukocyte recruitment and neointima formation, whereas endothelial overexpression of SOCS1 diminished arterial rejection. Induction of endothelial adhesion molecules in early stages of GA was suppressed by the VESOCS1 transgene and this effect was confirmed in cultured aortic ECs. Moreover, VESOCS1 maintained better vascular function during GA progression. Mechanistically, endothelial SOCS1, by modulating both basal and cytokine-induced expression of the adhesion molecules PECAM-1, ICAM-1 and VCAM-1, restrained leukocyte adhesion and trans-endothelial migration during inflammatory cell infiltration. SOCS1 prevents GA progression by preserving endothelial function and attenuating cytokine-induced adhesion molecule expression in vascular endothelium.
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影响因子：
9.3
作者：
Min W;Pober JS
通讯作者：
Pober JS
影响因子：
64.8
作者：
Tellides, G;Tereb, DA;Pober, JS
通讯作者：
Pober, JS
DOI：
10.1073/pnas.95.24.14395
发表时间：
1998-11-24
影响因子：
11.1
作者：
Starr, R;Metcalf, D;Alexander, WS
通讯作者：
Alexander, WS
影响因子：
5.3
作者：
Balabanov, Roumen;Strand, Krystal;Popko, Brian
通讯作者：
Popko, Brian
影响因子：
64.5
作者：
Marine, JC;Topham, DJ;Ihle, JN
通讯作者：
Ihle, JN