"Angiotensin II memory" contributes to the development of hypertension and vascular injury via activation of NADPH oxidase
"Angiotensin II memory" contributes to the development of hypertension and vascular injury via activation of NADPH oxidase
复制标题
“血管紧张素 II 记忆”通过 NADPH 氧化酶的激活促进高血压和血管损伤的发生
DOI：
10.1016/j.lfs.2016.02.037
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发表时间：
2016-03-15
期刊：
影响因子：
6.1
通讯作者：
Li, Hui-Hua
中科院分区：
文献类型：
--
作者：
Li, Wen-Jun;Liu, Ying;Li, Hui-Hua
目的：肾素-血管紧张素系统的激活在高血压及其并发症的发生发展中起着重要作用。我们以前的研究表明，细胞的“记忆”参与血管紧张素II（Ang II）诱导的心肌肥厚。本研究旨在探讨高浓度血管紧张素Ⅱ（Ang Ⅱ）逆转至正常状态对高血压及血管损伤的影响。通过主动脉环松弛研究、组织学分析、实时PCR和Western印迹分析来检查血管功能、炎症、氧化应激和血管生成。我们发现，持续高浓度Ang II输注3周，（Ang II 3 w）显著升高血压，增加主动脉壁厚度，胶原沉积，炎症，氧化应激，血管功能和p38 MAPK的活化，与生理盐水组相比，小鼠主动脉JNK 1/2、STAT 3和NF-κ B通路。高Ang II暴露2周，然后用生理盐水暴露1周（Ang II 2 + 1 w）未能逆转这些改变。这种现象被称为“代谢记忆”（或持续效应）。然而，在生理盐水输注过程中加入NADPH氧化酶抑制剂夹竹桃黄素（Ang Ⅱ 2 + 1 w + Apo）可显著改善这种有害作用。显著性：这些结果表明，我们首次报道了血管紧张素Ⅱ通过NADPH氧化酶介导的氧化应激的持续作用或“代谢记忆”在高血压和血管损伤中起重要作用。(C)2016 Elsevier Inc. All rights reserved.
Aims: Activation of the rennin-angiotensin systemplays a critical role in the development of hypertension and its complication. Our previous study has demonstrated that a cellular "memory" is involved in angiotensin II (Ang II)-induced cardiac hypertrophy. The aim of this study is to investigate the effect of reversal of high Ang II to normal condition on hypertension and vascular damage.Main methods: Wild-type male mice were randomly divided into five groups. The vascular function, inflammation, oxidative stress and angiogenesis were examined by aortic ring relaxation studies, histological analysis, real-time PCR and Western blot analysis.Key findings: We found that continuous high Ang II infusion for 3 weeks (Ang II 3w) significantly elevated blood pressure, increased aortic wall thickness, collagen deposition, inflammation, oxidative stress, vascular function and activation of p38 MAPK, JNK1/2, STAT3 and NF-kappa B pathways in mouse aorta compared with saline group. High Ang II exposure for 2 weeks followed by saline for 1 week (Ang II 2 + 1w) failed to reverse these alterations. This phenomenon was named "metabolic memory" (or persistent effect). However, addition of NADPH oxidase inhibitor apocynin during saline infusion (Ang II 2 + 1w + Apo) markedly ameliorated such deleterious effects.Significance: These results showed that we report the first that persistent effect or "metabolicmemory" of angiotensin II through NADPH oxidase-mediated oxidative stress plays important roles in hypertension and vascular injury. (C) 2016 Elsevier Inc. All rights reserved.