Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Pharmacol Ther. 2011 Oct;132(1):86-95. doi: 10.1016/j.pharmthera.2011.05.008. Epub 2011 Jun 12.
Alcoholic cardiomyopathy is manifested as cardiac hypertrophy, disrupted contractile function and myofibrillary architecture. An ample amount of clinical and experimental evidence has depicted a pivotal role for alcohol metabolism especially the main alcohol metabolic product acetaldehyde, in the pathogenesis of this myopathic state. Findings from our group and others have revealed that the mitochondrial isoform of aldehyde dehydrogenase (ALDH2), which metabolizes acetaldehyde, governs the detoxification of acetaldehyde formed following alcohol consumption and the ultimate elimination of alcohol from the body. The ALDH2 enzymatic cascade may evolve as a unique detoxification mechanism for environmental alcohols and aldehydes to alleviate the undesired cardiac anomalies in ischemia-reperfusion and alcoholism. Polymorphic variants of the ALDH2 gene encode enzymes with altered pharmacokinetic properties and a significantly higher prevalence of cardiovascular diseases associated with alcoholism. The pathophysiological effects of ALDH2 polymorphism may be mediated by accumulation of acetaldehyde and other reactive aldehydes. Inheritance of the inactive ALDH2*2 gene product is associated with a decreased risk of alcoholism but an increased risk of alcoholic complications. This association is influenced by gene-environment interactions such as those associated with religion and national origin. The purpose of this review is to recapitulate the pathogenesis of alcoholic cardiomyopathy with a special focus on ALDH2 enzymatic metabolism. It will be important to dissect the links between ALDH2 polymorphism and prevalence of alcoholic cardiomyopathy, in order to determine the mechanisms underlying such associations. The therapeutic value of ALDH2 as both target and tool in the management of alcoholic tissue damage will be discussed.
酒精性心肌病的表现为心肌肥厚、收缩功能障碍和肌原纤维结构紊乱。大量的临床和实验证据表明，酒精代谢，尤其是主要的酒精代谢产物乙醛，在这种肌病状态的发病机制中起着关键作用。我们小组和其他小组的研究结果表明，代谢乙醛的线粒体同工型醛脱氢酶（ALDH2）控制着饮酒后形成的乙醛的解毒作用，以及酒精从体内的最终消除。ALDH2 酶级联反应可能是环境中醇类和醛类的独特解毒机制，可减轻缺血再灌注和酒精中毒引起的不良心脏异常。ALDH2 基因的多态性变体编码具有改变的药代动力学特性的酶，并且与与酒精中毒相关的心血管疾病的发生率显著增加。ALDH2 多态性的病理生理效应可能是通过乙醛和其他反应性醛类的积累来介导的。无活性的 ALDH2*2 基因产物的遗传与酒精中毒风险降低有关，但与酒精性并发症的风险增加有关。这种关联受到基因-环境相互作用的影响，例如与宗教和民族起源有关的相互作用。本综述的目的是概述酒精性心肌病的发病机制，特别关注 ALDH2 酶代谢。解析 ALDH2 多态性与酒精性心肌病患病率之间的联系将是重要的，以确定这些关联的机制。将讨论 ALDH2 作为酒精性组织损伤管理的目标和工具的治疗价值。
