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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #143351
Title: CARDIAC OVEREXPRESSION OF ALCOHOL DEHYDROGENASE EXACERBATES CARDIAC CONTRACTILE DYSFUNCTION, LIPID PEROXIDATION, AND PROTEIN DAMAGE AFTER CHRONIC ETHANOL INGESTION

Author
item HINTZ, KADON - UNIV OF NORTH DAKOTA
item RELLING, DAVID - UNIV OF NORTH DAKOTA
item Saari, Jack
item BORGERDING, ANTHONY - UNIV OF NORTH DAKOTA
item DUAN, JINHONG - UNIV OF NORTH DAKOTA
item NORBY, FAYE - UNIV OF NORTH DAKOTA
item REN, BONNIE - UNIV OF NORTH DAKOTA
item KATO, KOSAI - UNIV OF NORTH DAKOTA
item EPSTEIN, PAUL - UNIV OF NORTH DAKOTA
item REN, JUN - UNIV OF NORTH DAKOTA

Submitted to: Alcoholism: Clinical and Experimental
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/1/2003
Publication Date: 7/1/2003
Citation: Hintz, K.K., Relling, D.P., Saari, J.T., Borgerding, A.J., Duan, J., Norby, F.L., Ren, B.H., Kato, K., Epstein, P.N., Ren, J. 2003. Cardiac overexpression of alcohol dehydrogenase exacerbates cardiac contractile dysfunction, lipid peroxidation, and protein damage after chronic ethanol ingestion. Alcoholism: Clinical and Experimental Research. 27(7):1090-1098.

Interpretive Summary: How chronic alcohol consumption causes heart daage is not well understood. One hypothesis is that damage is caused by acetaldehyde, a toxic by-product of alcohol metabolism. To test this hypothesis, effects of alcohol consumption in normal mice were compared to those in mice that gave genetically higher amounts in their hearts of the enzyme (ADH) that converts alcohol to acetaldehyde. Following long-term consumption of alcohol, heart cells from normal mice had depressed ability to contract, impaired release of the calcium that causes contraction and evidence of increased damage to protein and lipids. In heart cells from mice with elevated levels of ADH (and therefore of acetaldehyde) this impaired function and damage were exaggerated relative to normal mice. This increase in heart damage by an increase in heart acetaldehyde supports the view that acetaldehyde causes the heart damage of chronic alcohol consumption. These findings will be useful to scientists and consumers interested in the pathology associated with chronic alcohol consumption.

Technical Abstract: Alcoholic cardiomyopathy is manifested as ventricular dysfunction although its specific toxic mechanism(s) remains obscure. This study was designed to examine the impact of enhanced acetaldehyde (ACA) exposure on cardiac function via cardiac-specific over-expression of alcohol dehydrogenase (ADH) following alcohol intake. ADH transgenic and wild-type FVB mice were placed on a 4% alcohol or control diet for 8 wks. Mechanical and intracellular Ca**2+ properties were evaluated in cardiac myocytes. Levels of ACA, lipid peroxidation and protein carbonyl formation were determined. FVB and ADH mice consuming ethanol exhibited elevated blood ethanol/ACA, cardiac ACA and cardiac hypertrophy compared with non-ethanol consuming mice. However, the levels of cardiac ACA and hypertrophy were significantly greater in ADH ethanol fed mice than FVB ethanol fed mice. ADH transgene itself did not affect mechanical and intracellular Ca**2+ properties with the exception of reduced resting intracellular Ca**2+ and Ca**2+ re-sequestration at low pace frequency. Myocytes from ethanol-fed mice showed significantly depressed peak shortening, velocity of shortening/relengthening, Ca**2+-induced intracellular Ca**2+ release and SR Ca**2+ load associated with similar duration of shortening/relengthening compared to myocytes from control mice. Strikingly, the ethanol-induced mechanical and intracellular Ca**2+ defects were exacerbated in ADH myocytes compared to FVB group with the exception of velocity of shortening/relengthening. The lipid peroxidation end product malondialdehyde and protein carabonyl formation were significantly elevated in both livers and hearts following chronic ethanol consumption with the cardiac lipid and protein damage being exaggerated by ADH transgene. These data suggest that increased cardiac ACA exposure due to ADH transgene expression may play an important role in cardiac contractile dysfunctions associated with lipid and protein damage following alcohol intake.