...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Progressive hyperophy and heart failure in #beta#_1-adrenergic receptor transgenic mice
【24h】

Progressive hyperophy and heart failure in #beta#_1-adrenergic receptor transgenic mice

机译:#beta#_1-肾上腺素能受体转基因小鼠的进行性肥大和心力衰竭

获取原文
获取原文并翻译 | 示例
           

摘要

Stimulation of cardiac #beta#_1-adrenergic recep- tors is the main mechanism that increases heart rate and contractility. Consequently, several pharmacological and gene transfer strategies for the prevention of heart failure aim at improving the function of the cardiac #beta#-adrenergic receptor system, whereas current clinical treatment favors a reduction of cardiac stimulation. To address this controversy, we have generated mice with heart-specific overexpression of #beta#_1 adrenergic receptors. Their cardiac function was investigated in organ bath experiments as well as in vivo by cardiac catheterization and by time-resolved NMR imaging. The transgenic mice had increased cardiac contractility at a young age but also developed markcd myocyte hypertrophy (3.5-fold increase in myocyte area). This increasc was followed by progressive heart failure with functional and histological deficits typical for humans with heart failure. Contractility was reduced by approx=50 in 35-week-old mice, and ejection fraction was reduced down to a minimum of approx=20. We concludc that overexpression of #beta#_1-adrenergic receptors in the heart may lead to a short-lived improvement of car- diac function, but that increased #beta#_1-adrenergic receptor sig- nalling is ultimately detrimental.
机译:心脏#beta#_1-肾上腺素能受体的刺激是增加心率和收缩力的主要机制。因此,用于预防心力衰竭的几种药理学和基因转移策略旨在改善心脏#beta#-肾上腺素能受体系统的功能,而当前的临床治疗倾向于减少心脏刺激。为了解决这个争议,我们产生了具有心脏特异性#beta#_1肾上腺素能受体过度表达的小鼠。在器官浴实验中以及在体内通过心脏导管检查和时间分辨NMR成像研究了它们的心脏功能。转基因小鼠年轻时心脏收缩力增加,但也出现了明显的心肌细胞肥大(心肌细胞面积增加了3.5倍)。这种增加之后是进行性心力衰竭,伴有心力衰竭患者典型的功能和组织学缺陷。 35周龄小鼠的收缩力降低约50,射血分数降低至最小值约20。我们认为,心脏中#beta#_1-肾上腺素受体的过度表达可能会导致短暂的心脏功能改善,但是#beta#_1-肾上腺素受体信号的增加最终是有害的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号