Animal Model of Ethanol-Induced Cardiomyopathy

乙醇诱发的心肌病动物模型

• 批准号: 6949198
• 负责人: Judith K Gwathmey
• 金额: $ 97.08万
• 依托单位: GWATHMEY, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949198
• 关键词: Internet; alcoholism /alcohol abuse; animal colony; animal genetic material tag; cardiotoxin; chickens; clinical research; disease /disorder etiology; disease /disorder model; ethanol; functional /structural genomics; gene expression; gene expression profiling; genetic regulation; heart failure; heart function; histology; human genetic material tag; human tissue; model design /development; molecular pathology; myocardium disorder; patient oriented research; prognosis; western blottings

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.

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，仍然缺乏研究和了解的影响，对心力衰竭（HF）的发展。尽管酒精诱导的细胞改变和HF发展之间的关系尚不清楚，但存在真实的需要开发和表征动物模型，该动物模型显示与包括心力衰竭表型在内的多个水平的人AHF一致。本研究的目的是证明一个新建立的模型在多个水平上显示心脏功能的改变。我们将进一步确认在参与兴奋-收缩偶联的选定蛋白质水平上与人类状况的一致性。此外，我们将在我们的模型以及来自患有AHF的人类心脏的样本中鉴定失调基因。在第二阶段应用中，我们将开发几种产品（即定制印迹、AHF阵列、RNA、慢性HF动物、网站和数据库）以及交钥匙服务（AHF模型中的药物测试、ECHO、体内血液动力学测量）。我们的具体目标是：具体目标1：假设条件：酒精诱导的心力衰竭（AHF）将或将不会经历心功能不全的解决，在一些临床环境中报告的人类。心脏功能障碍可以在多个水平上表现出来，包括在分离的肌细胞水平上。具体目标二：假设：已知在其他病因如缺血性和特发性扩张型心肌病引起的心力衰竭中发生变化的蛋白质在禽AHF和人AHF中也会发生类似的变化。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导的心力衰竭样品中发现的失调基因高度一致。具体目标5：建立AHF动物群。为有兴趣研究我们的AHF动物模型的研究者建立一个信息和参考网站。在国家会议和期刊出版物上介绍鸟类AHF模型。销售产品，即交钥匙服务，定制印迹，AHF芯片阵列，RNA等。