NADPH oxidases mediate a cellular "memory" of angiotensin II stress in hypertensive cardiac hypertrophy
NADPH oxidases mediate a cellular "memory" of angiotensin II stress in hypertensive cardiac hypertrophy
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DOI：
10.1016/j.freeradbiomed.2013.08.179
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发表时间：
2013-12-01
影响因子：
7.4
通讯作者：
Li, Hui-Hua
中科院分区：
文献类型：
--
作者：
Wang, Hong-Xia;Yang, Hui;Li, Hui-Hua
糖尿病患者即使血糖正常，也会对高血糖应激产生长期的“记忆”。在这份报告中，我们提出了一个类似的假设，即暴露于连续高血管紧张素H（Ang II）的结果在细胞的“记忆”在离体心肌细胞和心脏组织，我们调查的作用，NADPH氧化酶在这种现象。连续高浓度Ang II 3天显著增加心肌细胞大小、TUNEL阳性凋亡心肌细胞、炎性细胞因子表达和氧化应激。在记忆条件下（高Ang II 2天，随后正常培养基1天）也观察到这些有害作用。此外，在小鼠模型中，与对照小鼠相比，Ang II输注3周显著增加了心脏肥大、凋亡、炎症和ROS生成，但降低了心脏功能，在记忆条件下的小鼠中也观察到类似的效果。重要的是，阻断NADPH氧化酶，夹竹桃苷减少诱导高血管紧张素II应激标志物在分离的心肌细胞和小鼠心脏。这些作用与抑制NADPH氧化酶介导的AKT/mTOR/S6 K和ERK信号通路有关。目前的结果证实了这样的假设，即暴露于持续高的Ang II导致高血压细胞记忆，即使当细胞或小鼠被切换回正常的Ang II时，这种记忆仍然存在。这种现象与NADPH氧化酶介导的氧化应激有关。(C)2013 Elsevier Inc. All rights reserved.
A long-term "memory" of hyperglycemic stress, even when glycemia is normalized, has been previously reported in diabetes. In this report we propose a similar hypothesis that exposure to continuous high angiotensin H (Ang II) results in a cellular "memory" in isolated cardiomyocytes and in the heart tissues, and we investigate the role of NADPH oxidases in this phenomenon. Continuous high Ang II for 3 days markedly increased cardiomyocyte size, TUNEL-positive apoptotic cardiomyocytes, expression of inflammatory cytokines, and oxidative stress. These deleterious effects were also observed in the memory condition (high Ang II for 2 days followed by normal medium for 1 day). Furthermore, in a mouse model, Ang II infusion for 3 weeks significantly increased cardiac hypertrophy, apoptosis, inflammation, and ROS generation but decreased cardiac function compared with control mice, and similar effects were also observed in mice in the memory condition. Importantly, blockade of NADPH oxidase using apocynin diminished the induction of high Ang II stress markers in isolated cardiomyocytes and in the mouse heart. These effects were associated with inhibition of NADPH oxidase-mediated AKT/mTOR/S6K and ERK signaling pathways. The present results demonstrate the hypothesis that exposure to continuous high Ang II results in a hypertensive cellular memory that remains, even when cells or mice are switched back to normal Ang II. This phenomenon was associated with NADPH oxidase-mediated oxidative stress. (C) 2013 Elsevier Inc. All rights reserved.