Beta-adrenergic adaptation in paediatric idiopathic dilated cardiomyopathy
Beta-adrenergic adaptation in paediatric idiopathic dilated cardiomyopathy
复制标题
DOI：
10.1093/eurheartj/ehs229
复制
发表时间：
2014-01-01
影响因子：
39.3
通讯作者：
Sucharov, Carmen C.
中科院分区：
文献类型：
--
作者：
Miyamoto, Shelley D.;Stauffer, Brian L.;Sucharov, Carmen C.
背景尽管成人心力衰竭（HF）的病理生理学和治疗已得到很好的研究，但对儿童HF的了解仍然很少。在成人中，肾上腺素能受体（AR）介导的适应在HF的心脏异常中起着核心作用，这些患者对β受体阻滞剂（BB）治疗反应良好。然而，在HF儿童中，越来越多的文献表明成人HF治疗缺乏疗效。由于这些意想不到的差异，在治疗反应和缺乏有关的儿科心脏的分子适应的数据，我们调查了HF在children.Methods和resultsExplanted成人和儿童特发性扩张型心肌病和非失败的控制心脏的分子特征在研究中使用。我们的研究结果表明，儿童HF的分子特征是显着不同的，从他们的成人同行。这些差异包括：（i）在儿童中下调（1）-和（2）-AR，而在成人中维持（2）-AR表达;（ii）在儿童中上调连接蛋白43，而在成人中观察到下调;（iii）磷酸酶表达无差异，而在成人中观察到上调;（iv）在儿童中Ser 16或Thr 17位点的受磷蛋白磷酸化没有降低，这是成人HF的已知特征。结论有一个不同的适应-HF儿童与成人的AR和肾上腺素能信号通路比较。我们的研究结果开始，以解决心血管研究的差异，具体到儿童，并建议，年龄相关的差异，在适应可能会影响对治疗的反应。这些发现可能会导致当代HF儿童管理的范式转变。
BackgroundAlthough the pathophysiology and treatment of adult heart failure (HF) are well studied, HF in children remains poorly understood. In adults, adrenergic receptor (AR)-mediated adaptation plays a central role in cardiac abnormalities in HF, and these patients respond well to -blocker (BB) therapy. However, in children with HF, there is a growing body of literature suggesting a lack of efficacy of adult HF therapies. Due to these unanticipated differences in response to therapy and the paucity of data regarding the molecular adaptation of the paediatric heart, we investigated the molecular characteristics of HF in children.Methods and resultsExplanted hearts from adults and children with idiopathic dilated cardiomyopathy and non-failing controls were used in the study. Our results show that the molecular characteristics of paediatric HF are strikingly different from their adult counterparts. These differences include: (i) down-regulation of (1)- and (2)-AR in children, whereas (2)-AR expression is maintained in adults; (ii) up-regulation of connexin43 in children, whereas down-regulation is observed in adults; (iii) no differences in phosphatase expression, whereas up-regulation is observed in adults; (iv) no decrease in the phosphorylation of phospholamban at the Ser16 or Thr17 sites in children, which are known characteristics of adult HF.ConclusionThere is a different adaptation of -AR and adrenergic signalling pathways in children with HF compared with adults. Our results begin to address the disparities in cardiovascular research specific to children and suggest that age-related differences in adaptation could influence the response to therapy. These findings could lead to a paradigm shift in the contemporary management of children with HF.