Animal Model of Ethanol-Induced Cardiomyopathy

点击翻译按钮获取中文摘要

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.