IGF-1 reduces inflammatory responses, suppresses oxidative stress, and decreases atherosclerosis progression in ApoE-deficient mice
IGF-1 reduces inflammatory responses, suppresses oxidative stress, and decreases atherosclerosis progression in ApoE-deficient mice
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DOI：
10.1161/atvbaha.107.156257
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发表时间：
2007-12-01
影响因子：
8.7
通讯作者：
Delafontaine, Patrick
中科院分区：
文献类型：
--
作者：
Sukhanov, Sergiy;Higashi, Yusuke;Delafontaine, Patrick
目的-尽管生长因子通过其刺激血管平滑肌细胞（VSMC）增殖和迁移的能力被认为在动脉粥样硬化的起始和进展中起允许的作用，但胰岛素样生长因子-1（IGF-1）的作用尚不清楚。在这里，我们报告的第一次，IGF-1输注减少动脉粥样硬化斑块的进展ApoE-缺陷小鼠在西方diet.Methods和结果-ApoE-null小鼠（8周）与车辆或重组人IGF-1和高脂肪饮食喂养12周。对主动脉窦的分析显示，IGF-1输注减少了动脉粥样硬化斑块的进展和巨噬细胞浸润到病变中。此外，IGF-1降低促炎细胞因子白细胞介素-6和肿瘤坏死因子-α的血管表达，降低主动脉超氧化物形成和尿8-异前列腺素水平，并增加主动脉pAkt和eNOS表达和循环内皮祖细胞，与抗氧化剂，结论-我们的数据表明，循环IGF-1的增加减少了血管炎症反应，全身和血管氧化应激并减少动脉粥样硬化斑块进展。这些发现对动脉粥样硬化的治疗具有重要意义。
Objective - Whereas growth factors, via their ability to stimulate vascular smooth muscle cell (VSMC) proliferation and migration, have been thought to play a permissive role in atherosclerosis initiation and progression, the role of insulin- like growth factor-1 (IGF-1) is unknown. Here we report for the first time that IGF-1 infusion decreased atherosclerotic plaque progression in ApoE-deficient mice on a Western diet.Methods and Results - ApoE-null mice (8 weeks) were infused with vehicle or recombinant human IGF-1 and fed a high-fat diet for 12 weeks. Analysis of aortic sinuses revealed that IGF-1 infusion decreased atherosclerotic plaque progression and macrophage infiltration into lesions. Furthermore, IGF-1 decreased vascular expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, reduced aortic superoxide formation and urinary 8- isoprostane levels, and increased aortic pAkt and eNOS expression and circulating endothelial progenitor cells, consistent with an antiinflammatory, antioxidant, and prorepair effect on the vasculature.Conclusions - Our data indicate that an increase in circulating IGF-1 reduces vascular inflammatory responses, systemic and vascular oxidant stress and decreases atherosclerotic plaque progression. These findings have major implications for the treatment of atherosclerosis.