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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Soluble Epoxide Hydrolase Plays An Essential Role In Angiotensin Il-induced Cardiac Hypertrophy
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Soluble Epoxide Hydrolase Plays An Essential Role In Angiotensin Il-induced Cardiac Hypertrophy

机译：可溶性环氧水解酶在血管紧张素II引起的心肌肥大中起重要作用

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摘要

Pathophysiological cardiac hypertrophy is one of the most common causes of heart failure. Epoxyeicosatrienoic acids, hydrolyzed and degraded by soluble epoxide hydrolase (sEH), can function as endothelium-derived hyperpolarizing factors to induce dilation of coronary arteries and thus are cardioprotective. In this study, we investigated the role of sEH in two rodent models of angiotensin Il (Ang Il)-induced cardiac hypertrophy. The protein level of sEH was elevated in the heart of both spontaneously hypertensive rats and Ang Il-infused Wistar rats. Blocking the Ang Il type 1 receptor with losartan could abolish this induction. Administration of a potent sEH inhibitor (sEHI) prevented the pathogenesis of the Ang Il-induced hypertrophy, as demonstrated by decreased left ventricular hypertrophy assessed by echocardiography, reduced cardiomyocyte size, and attenuated expression of hypertrophy markers, including atrial natriuretic factor and β-myosin heavy chain. Because sEH elevation was not observed in exercise- or norepinephrine-induced hypertrophy, the sEH induction was closely associated with Ang Il-induced hypertrophy. In vitro, Ang Il upregulated sEH and hypertrophy markers in neonatal cardiomy ocytes isolated from rat and mouse. Expression of these marker genes was elevated with adenovirus-mediated sEH overexpression but decreased with sEHI treatment. These results were supported by studies in neonatal cardiomyocytes from sEH~(-/-) mice. Our results suggest that sEH is specifically upregulated by Ang Il, which directly mediates Ang Il-induced cardiac hypertrophy. Thus, pharmacological inhibition of sEH would be a useful approach to prevent and treat Ang Il-induced cardiac hypertrophy.
机译：病理生理性心脏肥大是心力衰竭的最常见原因之一。被可溶性环氧化物水解酶（sEH）水解和降解的环氧二十碳三烯酸可起内皮衍生的超极化因子的作用，诱导冠状动脉扩张，因此具有心脏保护作用。在这项研究中，我们调查了sEH在血管紧张素II（Ang II）诱导的心肌肥大的两种啮齿动物模型中的作用。自发性高血压大鼠和注入Ang II的Wistar大鼠的心脏中sEH的蛋白质水平均升高。用氯沙坦阻断Ang II 1型受体可以消除这种诱导作用。强有力的sEH抑制剂（sEHI）的给药可预防Ang II诱导的肥大的发病机制，如超声心动图评估的左室肥大减少，心肌细胞大小减少以及肥大标志物（包括心钠素和β-肌球蛋白）的表达减弱所证明的那样。重链。因为在运动或去甲肾上腺素诱导的肥大中未观察到sEH升高，所以sEH诱导与Ang II诱导的肥大密切相关。在体外，Ang II上调了从大鼠和小鼠分离出的新生儿心肌细胞中的sEH和肥大标记。这些标记基因的表达随腺病毒介导的sEH过表达而升高，但随sEHI处理而降低。这些结果得到了来自sEH〜（-/-）小鼠的新生儿心肌细胞研究的支持。我们的结果表明，sEH被Ang II特异性上调，Ang II直接介导Ang II诱导的心脏肥大。因此，sEH的药理学抑制将是预防和治疗Ang II诱导的心脏肥大的有用方法。

著录项

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  • 作者

    Ding Ai; Wei Pang; Nan Li; Ming Xu; Paul D. Jones; Jun Yang; Youyi Zhang; Nipavan Chiamvimonvat; John Y.-J. Shyy; Bruce D. Hammock; Yi Zhu;

  • 作者单位

    Department of Physiology and Pathophysiology, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Health Science Center, Ministry of Education, Peking University, Beijing 100083, China Department of Entomology and Cancer Research Center, University of California Medical Center, University of California, Davis, CA 95616;

    Department of Physiology and Pathophysiology, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Health Science Center, Ministry of Education, Peking University, Beijing 100083, China;

    Department of Physiology and Pathophysiology, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Health Science Center, Ministry of Education, Peking University, Beijing 100083, China;

    Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Health Science Center, Ministry of Education, Peking University, Beijing 100083, China;

    Department of Entomology and Cancer Research Center, University of California Medical Center, University of California, Davis, CA 95616 International Flavors and Fragrances Inc., 1515 State Highway 36, Union Beach, NJ 07735;

    Department of Entomology and Cancer Research Center, University of California Medical Center, University of California, Davis, CA 95616;

    Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Health Science Center, Ministry of Education, Peking University, Beijing 100083, China;

    Department of Cardiovascular Medicine, University of California Medical Center, University of California, Davis, CA 95616;

    Division of Biomedical Sciences, University of California, Riverside, CA 92521;

    Department of Entomology and Cancer Research Center, University of California Medical Center, University of California, Davis, CA 95616;

    Department of Physiology and Pathophysiology, Peking University Third Hospital a;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    epoxyeicosatrienoic acid; cardiomyocyte; activator protein 1;

    机译：环氧二十碳三烯酸;心肌细胞;激活蛋白1;

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