Animal Model of Ethanol-Induced Cardiomyopathy

描述(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。尽管酗酒是一个主要的健康和社会问题，但关于酒精滥用对心力衰竭(HF)发展的影响，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的发生发展之间的关系尚不清楚，但确实需要开发和鉴定一种动物模型，表明与人类AHF的一致性是包括心力衰竭表型在内的多个水平。这项AHF研究的目的是证明一个新建立的模型在多个水平上显示了心功能的变化。我们将在参与兴奋-收缩偶联的选定蛋白的水平上进一步证实与人类状况的一致性。此外，我们将在我们的模型中以及AHF患者的心脏样本中识别非调控基因。在这个第二阶段的应用中，我们将开发几个产品(即定制的斑点、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、ECHO、体内血流动力学测量中的药物测试)。我们的具体目标是：特定目标1：假设：酒精诱导的心力衰竭(AHF)将会或将不会像某些临床环境中报道的那样经历心功能障碍的缓解。心功能障碍可以在多个水平上表现，包括在分离的心肌细胞水平上。特定目标2：假设：已知在其他原因引起的心力衰竭中改变的蛋白质，如缺血性和特发性扩张型心肌病，在禽类AHF和人类AHF中也将发生类似的变化。具体目标3：假设：酒精诱导的HF表型反映了参与兴奋-收缩偶联的基因的解除调控。具体目标4：在AHF动物心脏中发现的去调控基因将与在人类酒精诱导的心力衰竭样本中发现的去调控基因高度一致。具体目标5：建立急性出血热动物群体。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转介网站。在国家会议和期刊出版物上介绍禽类AHF模型。销售交钥匙服务、定制墨迹、AHF芯片阵列、RNA等产品。

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.