Animal Model of Ethanol-Induced Cardiomyopathy

描述（由申请人提供）：在西方国家，酒精引起的心力衰竭（AHF）约占所有心力​​衰竭病例的一半。尽管酗酒是一个重大的健康和社会问题，但对其对心力衰竭（HF）发展的影响的研究和了解仍然很少。尽管酒精诱导的细胞改变与心力衰竭发展之间的关系尚不清楚，但确实需要开发和表征动物模型，该模型在多个层面上与人类 AHF 一致，包括心力衰竭表型。这项 AHF 研究的目的是证明新建立的模型证明了心脏功能在多个层面上的改变。我们将进一步确认参与兴奋-收缩耦合的选定蛋白质水平与人类状况的一致性。此外，我们将在我们的模型以及患有 AHF 的人类心脏样本中识别失调的基因。在此第二阶段应用中，我们将开发多种产品（即定制印迹、AHF 阵列、RNA、慢性心力衰竭动物、网站和数据库）以及交钥匙服务（AHF 模型中的药物测试、ECHO、体内血流动力学测量）。我们的具体目标是： 具体目标 1：假设：正如一些人类临床环境中报道的那样，酒精引起的心力衰竭 (AHF) 会或不会出现心功能障碍的缓解。心脏功能障碍可以在多个水平上得到证明，包括在分离的肌细胞水平上。具体目标 2：假设：已知在其他病因（例如缺血性和特发性扩张型心肌病）心力衰竭中发生变化的蛋白质，在禽类 AHF 和人类 AHF 中也会发生类似变化。具体目标 3：假设：酒精诱导的心衰表型反映了参与兴奋-收缩耦合的基因失调。具体目标 4：在患有 AHF 的动物心脏中发现的失调基因将与在人类酒精诱发的心力衰竭样本中发现的失调基因高度一致。具体目标 5：建立 AHF 动物群体。为有兴趣研究我们的 AHF 动物模型的研究人员建立一个信息和推荐网站。在国家会议和期刊出版物上展示禽类 AHF 模型。销售产品，即交钥匙服务、定制印迹、AHF 芯片阵列、RNA 等。

DESCRIPTION (provided by applicant): Alcohol-induced heart failure (AHF) accounts for about half of all cases of heart failure in Western countries. Alcohol abuse, despite being a major health and social problem, remains poorly researched and understood in relation to the effects on the development of heart failure (HF). Although the relationship between alcohol-induced cellular alterations and the development of HF are unclear, there exists a real need for the development and characterization of an animal model that shows congruence with human AHF are multiple levels including the heart failure phenotype. The purpose of this study of AHF is to document that a newly established model demonstrates alterations in cardiac function at multiple levels. We will further confirm congruence with the human condition at the level of selected proteins involved in excitation-contraction coupling. Furthermore, we will identify deregulated genes in our model as well as in samples from human hearts with AHF. In this Phase 2 application we will develop several products (i.e. customized blots, AHF array, RNA, animals with chronic HF, a website, and database) as well as turnkey services (testing of drugs in AHF model, ECHO, in vivo hemodynamic measurements). Our specific aims are: Specific Aim 1: Hypotheses: Alcohol-induced heart failure (AHF) will or will not undergo resolution of cardiac dysfunction as reported in some clinical settings in humans. Cardiac dysfunction can be demonstrated at multiple levels including at the level of the isolated myocyte. Specific Aim 2: Hypothesis: Proteins known to be changed in heart failure from other etiologies such as ischemic and idiopathic dilated cardiomyopathy, will be similarly changed in avian AHF and human AHF. Specific Aim 3: Hypothesis: The alcohol-induced HF phenotype reflects deregulation of genes that are involved in excitation-contraction coupling. Specific Aim 4: Deregulated genes found in hearts from animals with AHF will be highly congruent with genes found to be deregulated in human alcohol induced heart failure samples. Specific Aim 5: Establish a colony of animals with AHF. Establish an information and referral website for Investigators interested in studying our animal model of AHF. Present the avian AHF model at national meetings and in journal publications. Sell products i.e. turnkey services, customized blots, AHF chip array, RNA etc.