Pro-inflammatory effect of fibrinogen and FDP on vascular smooth muscle cells by IL-6, TNF-α and iNOS
Pro-inflammatory effect of fibrinogen and FDP on vascular smooth muscle cells by IL-6, TNF-α and iNOS
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DOI：
10.1016/j.lfs.2011.03.003
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发表时间：
2011-05-09
期刊：
影响因子：
6.1
通讯作者：
Pang, Xiaoming
中科院分区：
文献类型：
--
作者：
Lu, Pei-pei;Liu, Jun-tian;Pang, Xiaoming
目的：动脉粥样硬化是动脉壁对多重内皮损伤的慢性炎症反应。纤维蛋白原作为炎症标志物之一，与动脉粥样硬化的发病机制密切相关。但是，纤维蛋白原的动脉粥样硬化是否与其对血管平滑肌细胞（VSMCs）的促炎作用有关尚不完全清楚。本研究旨在观察纤维蛋白原和纤维蛋白降解产物（FDP）对大鼠VSMCs中白细胞介素-6 （IL-6）、肿瘤坏死因子α (tnf - α)和诱导型一氧化氮合酶（iNOS）生成的影响。主要方法：培养大鼠VSMCs，用纤维蛋白原和FDP作为IL-6、tnf - α和iNOS的刺激剂。ELISA法检测上清液中IL-6、tnf - α水平，RT-PCR法检测IL-6、tnf - α、iNOS mRNA表达，western blot法和免疫细胞化学法检测iNOS蛋白表达。主要发现：纤维蛋白原和FOP均能显著刺激IL-6 mRNA和蛋白的表达。VSMCs中tnf - α和iNOS的时间和浓度依赖性。FOP的促炎效力高于纤维蛋白原，这似乎意味着较小的蛋白质片段具有更大的促炎活性。与iNOS相比，纤维蛋白原和FDP促进了更多的IL-6和tnf - α的蛋白表达，提示纤维蛋白原和FDP主要通过IL-6和tnf - α对VSMCs产生促炎作用。意义：这些发现有助于更好地了解纤维蛋白原对参与动脉粥样硬化的VSMCs的促炎作用，并提示针对动脉粥样硬化中高纤维蛋白原血症的治疗策略。(C) 2011爱思唯尔公司版权所有。
Aims: Atherosclerosis is a chronic inflammatory response of the arterial wall to multiple endothelial injuries. As one of the inflammatory markers, fibrinogen has been implicated in pathogenesis of atherosclerosis. But, it is not completely understood whether atherogenesis of fibrinogen is related to its pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe effects of fibrinogen and fibrin degradation products (FDP) on interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) generation in rat VSMCs.Main methods: Rat VSMCs were cultured, and fibrinogen and FDP were used as stimulants for IL-6, TNF-alpha, and iNOS. IL-6 and TNF-alpha level in the supernatant were measured by ELISA, mRNA expression of IL-6, TNF-alpha, and iNOS were assayed with RT-PCR, and protein expression of iNOS was detected with western blot and immunocytochemistry.Key findings: Fibrinogen and FOP both significantly stimulated mRNA and protein expressions of IL-6. TNF-alpha and iNOS in VSMCs in time- and concentration-dependent ways. The pro-inflammatory potency of FOP is higher than fibrinogen, which seems to mean that smaller fragments of the protein have greater proinflammatory activity. Fibrinogen and FDP promote more protein expressions of IL-6 and TNF-alpha compared to iNOS, suggesting that fibrinogen and FOP produce a pro-inflammatory effect on VSMCs mainly by IL-6 and TNF-alpha.Significance: These findings are helpful to better understand pro-inflammatory effect of fibrinogen on VSMCs involved in atherogenesis, and imply a therapeutic strategy targeting hyperfibrinogenemia in atherosclerosis. (C) 2011 Elsevier Inc. All rights reserved.