...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular and Cellular Cardiology >Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy.
【24h】

Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy.

机译：Polycystin-2突变导致心脏钙循环受损，并易患扩张型心肌病。

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

Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2), cause autosomal dominant polycystic kidney disease (ADPKD). Although the leading cause of mortality in ADPKD is cardiovascular disease, the relationship between these conditions remains poorly understood. PC2 is an intracellular calcium channel expressed in renal epithelial cells and in cardiomyocytes, and is thus hypothesized to modulate intracellular calcium signaling and affect cardiac function. Our first aim was to study cardiac function in a zebrafish model lacking PC2 (pkd2 mutants). Next, we aimed to explore the relevance of this zebrafish model to human ADPKD by examining the Mayo Clinic's ADPKD database for an association between ADPKD and idiopathic dilated cardiomyopathy (IDCM). Pkd2 mutant zebrafish showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. In human ADPKD patients, we found IDCM to coexist frequently with ADPKD. This association was strongest in patients with PKD2 mutations. Our results demonstrate that PC2 modulates intracellular calcium cycling, contributing to the development of heart failure. In human subjects we found an association between ADPKD and IDCM and suggest that PKD mutations contribute to the development of heart failure.
机译：PKD1和PKD2的突变（编码蛋白polycystin-1（PC1）和polycystin-2（PC2）的基因）引起常染色体显性遗传性多囊肾病（ADPKD）。尽管导致ADPKD死亡的主要原因是心血管疾病，但对这些疾病之间的关系仍然知之甚少。 PC2是在肾上皮细胞和心肌细胞中表达的细胞内钙通道，因此被认为可调节细胞内钙信号传导并影响心脏功能。我们的首要目标是在缺乏PC2（pkd2突变体）的斑马鱼模型中研究心脏功能。接下来，我们旨在通过检查Mayo Clinic的ADPKD数据库中ADPKD与特发性扩张型心肌病（IDCM）之间的关联，来探索这种斑马鱼模型与人类ADPKD的相关性。 Pkd2突变斑马鱼显示低心输出量和房室传导阻滞。孤立的pkd2突变体心脏显示受损的细胞内钙循环和钙交替蛋白。这些结果表明pkd2突变体中的心力衰竭。在人类ADPKD患者中，我们发现IDCM与ADPKD经常共存。在PKD2突变的患者中，这种关联最强。我们的结果表明，PC2调节细胞内钙循环，从而导致心力衰竭的发展。在人类受试者中，我们发现了ADPKD与IDCM之间的关联，并暗示PKD突变有助于心力衰竭的发展。

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