• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >A beneficial role of cardiac P2X4 receptors in heart failure: rescue of the calsequestrin overexpression model of cardiomyopathy.
【24h】

A beneficial role of cardiac P2X4 receptors in heart failure: rescue of the calsequestrin overexpression model of cardiomyopathy.

机译：心脏P2X4受体在心力衰竭中的有益作用：挽救心肌病的calsequestrin过表达模型。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The P2X4 purinergic receptor (P2X4R) is a ligand-gated ion channel. Its activation by extracellular ATP results in Ca2+ influx. Transgenic cardiac overexpression of the human P2X4 receptor showed an in vitro phenotype of enhanced basal contractility. The objective here was to determine the in vivo cardiac physiological role of this receptor. Specifically, we tested the hypothesis that this receptor plays an important role in modulating heart failure progression. Transgenic cardiac overexpression of canine calsequestrin (CSQ) showed hypertrophy, heart failure, and premature death. Crossing the P2X4R mouse with the CSQ mouse more than doubled the lifespan (182 +/- 91 days for the binary CSQ/P2X4R mouse, n = 35) of the CSQ mouse (71.3 +/- 25.4 days, n = 50, P < 0.0001). The prolonged survival in the binary CSQ/P2X4R mouse was associated with an improved left ventricular weight-to-body weight ratio and a restored beta-adrenergic responsiveness. The beneficial phenotype of the binary mouse was not associated with any downregulation of the CSQ level but correlated with improved left ventricular developed pressure and +/-dP/dt. The enhanced cardiac performance was manifested in young binary animals and persisted in older animals. The increased contractility likely underlies the survival benefit from P2X4 receptor overexpression. An increased expression or activation of this receptor may represent a new approach in the therapy of heart failure.
机译：P2X4嘌呤能受体（P2X4R）是配体门控离子通道。其被细胞外ATP激活导致Ca2 +大量涌入。人P2X4受体的转基因心脏过表达显示出增强的基础收缩力的体外表型。此处的目的是确定该受体在体内的心脏生理作用。具体来说，我们测试了这种受体在调节心力衰竭进展中起重要作用的假设。犬Calsequestrin（CSQ）的转基因心脏过表达显示肥大，心力衰竭和过早死亡。将P2X4R鼠标与CSQ鼠标交叉使用，使CSQ鼠标的寿命（71.3 +/- 25.4天，n = 50，P <71.3 +/- 25.4天，n <35）翻了一倍还多（二进制CSQ / P2X4R鼠标，n = 35为182 +/- 91天0.0001）。在二元CSQ / P2X4R小鼠中延长的生存期与改善的左心室体重比和恢复的β-肾上腺素能反应有关。二元小鼠的有益表型与CSQ水平的任何下调无关，但与改善的左心室发育压力和+/- dP / dt相关。在年轻的二元动物中表现出增强的心脏性能，在年长的动物中持续存在。收缩力的增加可能是P2X4受体过表达的生存获益的基础。该受体的表达或激活增加可能代表心力衰竭治疗的新方法。

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