Ethanol and acetaldehyde in alcoholic cardiomyopathy: from bad to ugly en route to oxidative stress.
Alcoholic cardiomyopathy is characterized by cardiomegaly, disruptions of myofibrillary architecture, reduced myocardial contractility, decreased ejection fraction, and enhanced risk of stroke and hypertension. Although several mechanisms have been postulated for alcoholic cardiomyopathy, including oxidative damage, accumulation of triglycerides, altered fatty acid extraction, decreased myofilament Ca(2+) sensitivity, and impaired protein synthesis, neither the mechanism nor the ultimate toxin has been unveiled. Primary candidates acting as specific toxins of myocardial tissue are ethanol; its first and major metabolic product, acetaldehyde; and fatty acid ethyl esters. Acetaldehyde has been demonstrated to impair directly cardiac contractile function, disrupt cardiac excitation-contractile coupling, and contribute to oxidative damage and lipid peroxidation. Acetaldehyde-elicited cardiac dysfunction may be mediated through cytochrome P450 oxidase, xanthine oxidase, and the stress-signaling cascade. Unfortunately, the most direct approach that can be used to examine toxicity is hampered by the fact that direct intake of acetaldehyde is highly toxic and unsuitable for long-term study. To overcome this obstacle, transgenic mice have been used to alter artificially ethanol/acetaldehyde metabolism, resulting in elevated acetaldehyde concentrations after ethanol ingestion. In this review, we summarize results obtained with the use of transgenic animal models to elucidate the role of acetaldehyde in the mechanism of action in alcoholic cardiomyopathy.
Division of Pharmaceutical Sciences, Graduate Neuroscience Program, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071-3375, USA.
Xiaochun
X
Zhang
Shi-Yan
SY
Li
Ricardo A
RA
Brown
Jun
J
Ren
D000079:Acetaldehyde / Q000633:toxicity*; D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
D000431:Ethanol; D000079:Acetaldehyde