Effects of chronic alcohol consumption on cardiac inflammation and fibrosis

长期饮酒对心脏炎症和纤维化的影响

• 批准号: 8254667
• 负责人: Brittany Ann Elliott
• 金额: $ 2.93万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8254667
• 关键词: Address; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic Cardiomyopathy; Alcoholism; Alcohols; Animal Model; Animals; Bone Marrow; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cardiovascular system; Cell Culture System; Cells; Cellular biology; Chronic; Congestive Heart Failure; Connective Tissue; Country; Disease; Doctor of Philosophy; Exposure to; Extracellular Matrix Proteins; Fibroblasts; Fibrosis; Foundations; Gastrointestinal tract structure; Gene Expression; Goals; Growth; Health; Health Care Costs; Heart; Heart Diseases; Heart Hypertrophy; Heart failure; Heavy Drinking; Human; Hypertrophy; In Vitro; Individual; Inflammation; Inflammatory; Inflammatory Response; Kidney; Knowledge; Laws; Lead; Light; Liver; Molecular; Molecular Biology Techniques; Myocardium; Myofibroblast; Organ; Pancreas; Play; Population; Principal Investigator; Recording of previous events; Research; Role; Scientist; Societies; Structure; System; Techniques; Testing; Tissues; Training; United States; Ventricular Remodeling; alcohol abuse therapy; alcohol effect; alcohol exposure; alcohol measurement; alcohol response; body system; cell transformation; cell type; chronic alcohol ingestion; design; experience; gene function; insight; mast cell; meetings; mouse model; pre-doctoral; problem drinker; research study; response; skills; stellate cell; young adult

Despite extensive knowledge of the deleterious effects of chronic alcohol abuse, alcoholism and its associated health issues remain a substantial problem. Approximately 14 million individuals in the United States alone battle alcohol addiction. Alcohol dependence and abuse result in over 200 billion dollars in health care costs annually in the United States. Chronic alcohol abuse results in damage to most organs and contributes to over 60 diseases. Extensive research has shown that liver and pancreas disease in response to alcohol abuse involves excessive accumulation of connective tissue or fibrosis. In these organs, resident stellate cells (and likely other cell populations like bone marrow-derived cells) are transformed into myofibroblasts, which actively participate in tissue remodeling through the secretion of extracellular matrix proteins. It appears that persistent inflammation induced by excessive alcohol consumption plays a role in the formation of myofibroblasts and subsequent fibrosis. Long-term alcohol abuse also leads to heart disease termed alcoholic cardiomyopathy. Much less is known about the progression of alcohol damage in the heart compared to that in many other organs. It is clear that alcohol and its metabolites can directly affect the function of cardiac muscle cells. The contribution of other cell types to the damaging effects of alcohol on the heart is not clear. We propose that chronic alcohol abuse elicits an adaptive response that includes cardiac hypertrophy (growth), fibrosis and inflammation. This initially adaptive response eventually results in decompensation of the heart with the ultimate consequence being that the heart is unable to meet the demands of the body. The long-term goal of the proposed study is to elucidate the mechanisms whereby chronic alcohol abuse results in alcoholic cardiomyopathy. The aim of the present study is to utilize a cell culture system to determine the effects of alcohol exposure on heart fibroblasts and inflammatory cells. These studies will provide important new information regarding the response of the heart and its cells to alcohol. These studies will also provide an excellent venue for the training of the principal investigator in molecular, cellular and whole animal techniques needed to investigate the mechanisms of alcohol-induced tissue damage.

尽管有广泛了解慢性酒精滥用的有害影响，但酒精中毒及其相关的健康问题仍然是一个重大的问题。仅在美国，大约有1400万人与酗酒。在美国，酒精依赖和滥用导致每年超过2000亿美元的医疗保健费用。慢性酒精滥用会对大多数器官造成损害，并导致60多种疾病。广泛的研究表明，肝脏和胰腺疾病响应酗酒，涉及结缔组织或纤维化的过度积累。在这些器官中，常驻星状细胞（以及可能的其他细胞群（如骨髓衍生细胞））转化为肌纤维细胞，这些细胞通过细胞外基质蛋白的分泌积极参与组织重塑。似乎过量饮酒引起的持续性炎症在肌纤维细胞的形成和随后的纤维化中起作用。长期酗酒也导致心脏病称为酒精性心肌病。与许多其他器官相比，关于酒精损害的进展知之甚少。显然，酒精及其代谢产物可以直接影响心肌细胞的功能。其他细胞类型对酒精对心脏的破坏性影响的贡献尚不清楚。我们建议慢性酒精滥用会引起自适应反应，其中包括心脏肥大（生长），纤维化和炎症。最初的适应性反应最终导致心脏不足，最终的后果是心脏无法满足身体的需求。拟议的研究的长期目标是阐明慢性酒精滥用导致酒精性心肌病的机制。本研究的目的是利用细胞培养系统来确定酒精暴露对心脏成纤维细胞和炎症细胞的影响。这些研究将提供有关心脏及其细胞对酒精的反应的重要新信息。这些研究还将为培训主要研究者在分子，细胞和整个动物技术中培训所需的主要研究者，以研究酒精诱导的组织损伤的机制。