Fingerprint profile of alcohol-associated heart failure in human hearts
Fingerprint profile of alcohol-associated heart failure in human hearts
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DOI：
10.1111/j.1530-0277.2008.00628.x
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发表时间：
2008-05-01
影响因子：
3.2
通讯作者：
Gwathmey, Judith K.
中科院分区：
文献类型：
--
作者：
Haddad, Georges E.;Saunders, Lori;Gwathmey, Judith K.
背景：过量饮酒被认为是左心室功能障碍的一个原因，并常常导致酒精性心力衰竭。据认为，所有扩张型心肌病病例中有 36% 是由于过量饮酒造成的。此外，由于慢性饮酒是一种社会行为，临床上并不总是清楚地自我报告，因此很难诊断酒精引起的心力衰竭与特发性扩张型心肌病（IDCM）引起的心力衰竭。有趣的是，这两种疾病都与左心室功能障碍和充血性心力衰竭有关。方法：我们从非衰竭和衰竭的人类心脏中创建了用于 IDCM 的人类心力衰竭 cDNA 阵列。该阵列包含 1,143 个心脏特异性寡核苷酸探针。该芯片用于筛选患有酒精相关心力衰竭的移植受者和器官捐献者的 RNA 样本。结果：我们的研究表明，酒精引起的心力衰竭具有失调基因的“特定指纹”特征。该特征可以区分纯酒精引起的心力衰竭患者和以酒精为并发症或促成因素的 IDCM 心力衰竭患者。此外，基因失调的模式表明基质、细胞骨架和结构蛋白的变化在过量饮酒引起的临床心力衰竭的发展中发挥着关键作用。 结论：我们首次报告了与人类酒精诱发的心力衰竭相关的失调基因的基因组“指纹”图谱。我们的结论是，酒精引起的人类心力衰竭的发病机制可能与结构（例如细胞骨架）、基质和/或结构蛋白的变化有关。停止饮酒后疾病的可逆性使其成为一种可能的发病机制。然而，在某个时刻，细胞外和细胞的变化会导致不可逆的心力衰竭。
Background: Excessive alcohol consumption is recognized as a cause of left ventricular dysfunction and leads often to alcohol-induced heart failure. It is thought that 36% of all cases of dilated cardiomyopathy are due to excessive alcohol intake. In addition, since chronic alcohol-consumption is a social behavior that is not always clearly self-reported clinically, it has been difficult to diagnose alcohol-induced heart failure versus heart failure due to idiopathic dilated cardiomyopathy (IDCM). Interestingly, both diseases are associated with left ventricular dysfunction and congestive heart failure.Methods: We have created a human heart failure cDNA array for IDCM from nonfailing and failing human hearts. The array contains 1,143 heart specific oligonucleotide probes. This array was used to screen RNA samples from transplant recipients and organ donors with alcohol-related heart failure.Results: Our study shows that alcohol-induced heart failure has a "specific fingerprint" profile of de-regulated genes. This profile can differentiate patients with pure alcohol-induced heart failure from patients with heart failure from IDCM with alcohol as a complicating or contributing factor. Furthermore, the pattern of gene de-regulation suggests a pivotal role for changes in matrix, cytoskeletal, and structural proteins in the development of clinical heart failure resulting from excessive alcohol consumption.Conclusions: We report for the first time a genomic "fingerprint" profile of de-regulated genes associated with human alcohol-induced heart failure. We conclude that the pathogenesis of alcohol-induced heart failure in humans is likely related to changes in architectural (e.g. cytoskeletal), matrix, and/or structural proteins. The reversibility of the disease upon cessation of alcohol consumption makes this a likely pathogenetic mechanism. Nevertheless, there is a point at which extracellular as well as cellular changes result in irreversible heart failure.