A Transgenic Model of Acetaldehyde Overproduction Accelerates Alcohol Cardiomyopathy

Chronic alcohol consumption produces alcoholic heart muscle disease (AHMD), a prevalent form of congestive heart failure. Several hypotheses have been proposed to explain the damaging effects of alcohol on the heart, but neither the mechanism nor the ultimate toxin has been established. In this stud...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 1999-11, Vol.291 (2), p.766
Main Authors: Liang, Q, Carlson, E C, Borgerding, A J, Epstein, P N
Format: Article
Language:English
Subjects:
Acetaldehyde - metabolism
Actins - genetics
Animals
Atrial Natriuretic Factor - genetics
Cardiomegaly - chemically induced
Cardiomyopathy, Alcoholic - etiology
Disease Models, Animal
Ethanol - pharmacology
L-Lactate Dehydrogenase - genetics
Mice
Mice, Transgenic
Microscopy, Electron
Myocardial Contraction - drug effects
NAD - analysis
RNA, Messenger - genetics
Time Factors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chronic alcohol consumption produces alcoholic heart muscle disease (AHMD), a prevalent form of congestive heart failure. Several hypotheses have been proposed to explain the damaging effects of alcohol on the heart, but neither the mechanism nor the ultimate toxin has been established. In this study, we use transgenic overexpression of alcohol dehydrogenase to elevate cardiac exposure to acetaldehyde, the major and most reactive metabolite of alcohol. Overexpression of alcohol dehydrogenase by 40-fold produced no detectable deleterious effects to the heart in the absence of alcohol. In the presence of alcohol, transgenic hearts contained 4-fold higher acetaldehyde than control hearts. Chronic alcohol exposure produced many changes similar to AHMD in transgenic hearts. Compared with control hearts, these pathological changes occurred more rapidly and to a greater extent: alcohol-exposed transgenic hearts were almost twice as large as control hearts. They demonstrated ultrastructural damage consistent with AHMD and had much lower contractility than alcohol-exposed control hearts. In addition, the transgenic hearts showed greater changes in mRNA expression for α-skeletal actin and atrial natriuretic factor than alcohol-exposed control hearts. Alterations in NAD + /NADH levels were insufficient to account for such severe damage in cardiomyopathic hearts. The increased damage produced in transgenic hearts suggests an important role for acetaldehyde in AHMD.
ISSN:0022-3565
1521-0103