Novel proteins associated with human dilated cardiomyopathy: selective reduction in α(1A)-adrenergic receptors and increased desensitization proteins.
Novel proteins associated with human dilated cardiomyopathy: selective reduction in α(1A)-adrenergic receptors and increased desensitization proteins.
复制标题
DOI：
10.3109/10799893.2013.764897
复制
发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Perez DM
中科院分区：
文献类型：
--
作者：
Shi T;Moravec CS;Perez DM
治疗人类心力衰竭的疗法以及与心力衰竭相关的蛋白质的鉴定仍然有限。我们分析了人类心力衰竭中的α1-肾上腺素能受体亚型，并对更均匀的样本进行蛋白质组学分析，以鉴定与人类心力衰竭相关的新蛋白质。对六个患有终末期扩张型心肌病的衰竭心脏和四个非衰竭心脏对照进行蛋白质组学分析。在48个鉴定的蛋白质中，26个蛋白质在样品之间是冗余的。这26种蛋白质中有10种以前被报道与心力衰竭有关。在新鉴定的蛋白质中，我们发现了几个肌肉蛋白和线粒体/电子传递蛋白，而新的功能与以前的报道相似。然而，我们也发现了新的蛋白质参与功能类别，如β-氧化和G-蛋白偶联受体信号传导和脱敏，以前与心力衰竭无关。我们还对心脏样本进行了放射性配体结合研究，证实了终末期扩张型心肌病中β1-肾上腺素能受体的大量丢失，但也发现了先前未报道的α 1A-肾上腺素能受体亚型的选择性降低。我们已经确定了与终末期扩张型心肌病相关的新蛋白质和功能类别。我们还报道，与先前表征的心力衰竭中β1-肾上腺素能受体的丧失相似，也存在α 1A-肾上腺素能受体的伴随丧失，α 1A-肾上腺素能受体被认为是心脏保护蛋白。
Therapeutics to treat human heart failure and the identification of proteins associated with heart failure are still limited. We analyzed α1-adrenergic receptor subtypes in human heart failure and performed proteomic analysis on more uniform samples to identify novel proteins associated with human heart failure. Six failing hearts with end-stage dilated cardiomyopathy and four non-failing heart controls were subjected to proteomic analysis. Out of 48 identified proteins, 26 proteins were redundant between samples. 10 of these 26 proteins were previously reported to be associated with heart failure. Of the newly identified proteins, we found several muscle proteins and mitochondrial/electron transport proteins, while novel were functionally similar to previous reports. However, we also found novel proteins involved in functional classes such as β-oxidation and G-protein coupled receptor signaling and desensitization not previously associated with heart failure. We also performed radioligand-binding studies on the heart samples and confirmed a large loss of β1-adrenergic receptors in end-stage dilated cardiomyopathy but also found a selective decrease in the α1A-adrenergic receptor subtype not previously reported. We have identified new proteins and functional categories associated with end-stage dilated cardiomyopathy. We also report that similar to the previously characterized loss of β1-adrenergic receptors in heart failure, there is also a concomitant loss of α1A-adrenergic receptors, which are considered cardioprotective proteins.
登录
查看更多内容
影响因子：
5.7
作者：
Abraham, WT;Gilbert, EM;Bristow, MR
通讯作者：
Bristow, MR
影响因子：
8.9
作者：
de Weger, Roel A.;Schipper, Marguerite E. I.;Bovenschen, Niels
通讯作者：
Bovenschen, Niels
影响因子：
39.3
作者：
KNECHT, M;REGITZZAGROSEK, V;FLECK, E
通讯作者：
FLECK, E
影响因子：
3
作者：
BOHM, M;DIET, F;ERDMANN, E
通讯作者：
ERDMANN, E
影响因子：
8.9
作者：
Grigore, A;Poindexter, B;Bick, RJ
通讯作者：
Bick, RJ