Mechanisms of alcoholic heart disease.
Mechanisms of alcoholic heart disease.
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DOI：
10.1177/1753944708095137
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发表时间：
2008-12-01
影响因子：
2.3
通讯作者：
Wold, Loren E
中科院分区：
文献类型：
--
作者：
Ren, Jun;Wold, Loren E
心脏功能受损在长期饮酒患者中常见，通常表现为心脏肥大、心肌收缩力降低（伴随射血分数和每搏输出量降低）、心肌纤维化、卒中和高血压风险增加以及心肌结构破坏。酒精性心肌病的发生机制包括氧化损伤、甘油三酯沉积、脂肪酸提取改变、肌丝Ca（2+）敏感性降低和蛋白质合成受损。然而，根本机制尚未阐明。几种酒精代谢物已被确定为心肌组织的特定毒素，包括乙醇，其第一个和主要的代谢产物-乙醛-和脂肪酸乙酯。乙醛直接损害心脏收缩功能，破坏心脏兴奋-收缩偶联，促进氧化损伤和脂质过氧化。不幸的是，最直接的研究方法（直接给予乙醛）是不可能的，因为直接摄入乙醛是高毒性的，不适合慢性研究。为了克服这一障碍，最近已经产生了转基因小鼠，以人为地改变乙醇/乙醛代谢，导致乙醇摄入后乙醛水平升高。本文将总结酒精性心肌病的一些假设机制，特别强调动物模型。
Compromised heart function is regularly seen in patients with chronic alcohol ingestion and is often manifested as cardiomegaly, reduced myocardial contractility (with concomitant reductions in ejection fraction and stroke volume), myocardial fibrosis, enhanced risk of stroke and hypertension, and disruptions in the myofibrillary structure. A number of mechanisms including oxidative damage, deposition of triglycerides, altered fatty acid extraction, decreased myofilament Ca(2+) sensitivity, and impaired protein synthesis have been proposed for the development of alcoholic cardiomyopathy. Nonetheless, the underlying mechanism(s) has not been delineated. Several alcohol metabolites have been identified as specific toxins of myocardial tissue, including ethanol, its first and major metabolic product--acetaldehyde--and fatty acid ethyl esters. Acetaldehyde directly impairs cardiac contractile function, disrupts cardiac excitation-contraction coupling and promotes oxidative damage and lipid peroxidation. Unfortunately, the most direct approach to studying this (direct administration of acetaldehyde) is impossible, since direct intake of acetaldehyde is highly toxic and unsuitable for chronic studies. In order to overcome this obstacle, transgenic mice have recently been produced to artificially alter ethanol/acetaldehyde metabolism, resulting in elevated acetaldehyde levels after ethanol ingestion. This review will summarize some of the postulated mechanisms for alcoholic cardiomyopathy, with special emphasis on animal models.