ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications.
ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications.
复制标题
DOI：
10.1016/j.pharmthera.2011.05.008
复制
发表时间：
2011-10
影响因子：
13.5
通讯作者：
Ren, Jun
中科院分区：
文献类型：
--
作者：
Zhang, Yingmei;Ren, Jun
酒精性心肌病表现为心肌肥厚、收缩功能和心肌结构紊乱。大量的临床和实验证据已经描述了酒精代谢，特别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的关键作用。我们小组和其他人的研究结果表明，代谢乙醛的乙醛脱氢酶（ALDH 2）的线粒体亚型控制着酒精消耗后形成的乙醛的解毒和酒精从体内的最终消除。ALDH 2酶级联反应可能作为一种独特的解毒机制，对环境中的酒精和醛，以减轻不希望的心脏异常缺血再灌注和酒精中毒。ALDH 2基因的多态性变体编码具有改变的药代动力学特性的酶，并且与酒精中毒相关的心血管疾病的患病率显著较高。ALDH 2多态性的病理生理效应可能是由乙醛和其他活性醛的积累介导的。非活性ALDH 2 *2基因产物的遗传与酒精中毒风险降低但酒精并发症风险增加相关。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基因-环境相互作用。本文综述了酒精性心肌病的发病机制，特别关注ALDH 2的酶代谢。重要的是要剖析ALDH 2多态性和酒精性心肌病患病率之间的联系，以确定这种关联的机制。ALDH 2作为靶点和工具在酒精性组织损伤的治疗价值将被讨论。
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.
登录
查看更多内容
影响因子：
3.2
作者：
Brown, R A;Anthony, M J;Ren, J
通讯作者：
Ren, J
影响因子：
9.3
作者：
Budas, Grant R.;Disatnik, Marie-Helene;Mochly-Rosen, Dana
通讯作者：
Mochly-Rosen, Dana
影响因子：
2.3
作者：
BROWN, RA;CARPENTIER, RG
通讯作者：
CARPENTIER, RG
影响因子：
10.8
作者：
Budas GR;Churchill EN;Disatnik MH;Sun L;Mochly-Rosen D
通讯作者：
Mochly-Rosen D
影响因子：
5.1
作者：
Chen, Yi-Chyan;Peng, Giia-Sheun;Yin, Shih-Jiun
通讯作者：
Yin, Shih-Jiun