Animal Model of Ethanol-Induced Cardiomyopathy

描述（由申请人提供）：在西方国家，酒精性心力衰竭（AHF）约占所有心力衰竭病例的一半。酒精滥用，尽管是一个主要的健康和社会问题，但对其对心力衰竭（HF）发展的影响的研究和理解仍然很少。尽管酒精诱导的细胞改变与心衰发展之间的关系尚不清楚，但确实需要开发和表征一种动物模型，该模型在包括心力衰竭表型在内的多个水平上与人类AHF一致。本研究的目的是证明一个新建立的模型显示心功能在多个水平上的改变。我们将进一步确认在参与兴奋-收缩耦合的选定蛋白质水平上与人类条件的一致性。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不受管制的基因。在这个二期申请中，我们将开发几种产品（即定制的印迹、AHF阵列、RNA、慢性HF动物、网站和数据库）以及交钥匙服务（AHF模型药物测试、ECHO、体内血流动力学测量）。我们的具体目的是：具体目的1：假设：在一些人类临床环境中，酒精性心力衰竭（AHF）会或不会经历心功能障碍的解决。心功能障碍可以在多个水平表现出来，包括在分离的心肌细胞水平。特定目的2：假设：已知在其他病因（如缺血性和特发性扩张型心肌病）心力衰竭中发生改变的蛋白质，将在禽AHF和人AHF中发生类似的改变。假设：酒精诱导的HF表型反映了参与兴奋-收缩耦合的基因的解除管制。特异性目标4：在AHF动物心脏中发现的不受调控的基因将与在人类酒精诱导的心力衰竭样本中发现的不受调控的基因高度一致。具体目标5：建立一个患有AHF的动物群体。为有兴趣研究AHF动物模型的研究者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AHF模型。销售产品，如交钥匙服务，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.