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.