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Cardiac overexpression of alcohol dehydrogenase exacerbates cardiac contractile dysfunction, lipid peroxidation, and protein damage after chronic ethanol ingestion.
Alcohol Clin Exp Res. 2003 Jul; 27(7):1090-8.AC

Abstract

BACKGROUND

Alcoholic cardiomyopathy is manifested as ventricular dysfunction, although its specific toxic mechanism remains obscure. This study was designed to examine the impact of enhanced acetaldehyde exposure on cardiac function via cardiac-specific overexpression of alcohol dehydrogenase (ADH) after alcohol intake.

METHODS

ADH transgenic and wild-type FVB mice were placed on a 4% alcohol or control diet for 8 weeks. Mechanical and intracellular Ca2+ properties were evaluated in cardiac myocytes. Levels of acetaldehyde, lipid peroxidation, and protein carbonyl formation were determined.

RESULTS

FVB and ADH mice consuming ethanol exhibited elevated blood ethanol/acetaldehyde, cardiac acetaldehyde, and cardiac hypertrophy compared with non-ethanol-consuming mice. However, the levels of cardiac acetaldehyde and hypertrophy were significantly greater in ADH ethanol-fed mice than FVB ethanol-fed mice. ADH transgene itself did not affect mechanical and intracellular Ca2+ properties with the exception of reduced resting intracellular Ca2+ and Ca2+ re-sequestration at low pace frequency. Myocytes from ethanol-fed mice showed significantly depressed peak shortening, velocity of shortening/relengthening, rise of intracellular Ca2+ transients, and sarco(endo)plasmic reticulum Ca2+ load associated with similar duration of shortening/relengthening compared with myocytes from control mice. Strikingly, the ethanol-induced mechanical and intracellular Ca2+ defects were exacerbated in ADH myocytes compared with the FVB group except velocity of shortening/relengthening. The lipid peroxidation end products malondialdehyde and protein carbonyl formation were significantly elevated in both livers and hearts after chronic ethanol consumption, with the cardiac lipid and protein damage being exaggerated by ADH transgene.

CONCLUSION

These data suggest that increased cardiac acetaldehyde exposure due to ADH transgene may play an important role in cardiac contractile dysfunctions associated with lipid and protein damage after alcohol intake.

Authors+Show Affiliations

Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

12878915

Citation

Hintz, Kadon K., et al. "Cardiac Overexpression of Alcohol Dehydrogenase Exacerbates Cardiac Contractile Dysfunction, Lipid Peroxidation, and Protein Damage After Chronic Ethanol Ingestion." Alcoholism, Clinical and Experimental Research, vol. 27, no. 7, 2003, pp. 1090-8.
Hintz KK, Relling DP, Saari JT, et al. Cardiac overexpression of alcohol dehydrogenase exacerbates cardiac contractile dysfunction, lipid peroxidation, and protein damage after chronic ethanol ingestion. Alcohol Clin Exp Res. 2003;27(7):1090-8.
Hintz, K. K., Relling, D. P., Saari, J. T., Borgerding, A. J., Duan, J., 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), 1090-8.
Hintz KK, et al. Cardiac Overexpression of Alcohol Dehydrogenase Exacerbates Cardiac Contractile Dysfunction, Lipid Peroxidation, and Protein Damage After Chronic Ethanol Ingestion. Alcohol Clin Exp Res. 2003;27(7):1090-8. PubMed PMID: 12878915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac overexpression of alcohol dehydrogenase exacerbates cardiac contractile dysfunction, lipid peroxidation, and protein damage after chronic ethanol ingestion. AU - Hintz,Kadon K, AU - Relling,David P, AU - Saari,Jack T, AU - Borgerding,Anthony J, AU - Duan,Jinhong, AU - Ren,Bonnie H, AU - Kato,Kosai, AU - Epstein,Paul N, AU - Ren,Jun, PY - 2003/7/25/pubmed PY - 2004/3/12/medline PY - 2003/7/25/entrez SP - 1090 EP - 8 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 27 IS - 7 N2 - BACKGROUND: Alcoholic cardiomyopathy is manifested as ventricular dysfunction, although its specific toxic mechanism remains obscure. This study was designed to examine the impact of enhanced acetaldehyde exposure on cardiac function via cardiac-specific overexpression of alcohol dehydrogenase (ADH) after alcohol intake. METHODS: ADH transgenic and wild-type FVB mice were placed on a 4% alcohol or control diet for 8 weeks. Mechanical and intracellular Ca2+ properties were evaluated in cardiac myocytes. Levels of acetaldehyde, lipid peroxidation, and protein carbonyl formation were determined. RESULTS: FVB and ADH mice consuming ethanol exhibited elevated blood ethanol/acetaldehyde, cardiac acetaldehyde, and cardiac hypertrophy compared with non-ethanol-consuming mice. However, the levels of cardiac acetaldehyde and hypertrophy were significantly greater in ADH ethanol-fed mice than FVB ethanol-fed mice. ADH transgene itself did not affect mechanical and intracellular Ca2+ properties with the exception of reduced resting intracellular Ca2+ and Ca2+ re-sequestration at low pace frequency. Myocytes from ethanol-fed mice showed significantly depressed peak shortening, velocity of shortening/relengthening, rise of intracellular Ca2+ transients, and sarco(endo)plasmic reticulum Ca2+ load associated with similar duration of shortening/relengthening compared with myocytes from control mice. Strikingly, the ethanol-induced mechanical and intracellular Ca2+ defects were exacerbated in ADH myocytes compared with the FVB group except velocity of shortening/relengthening. The lipid peroxidation end products malondialdehyde and protein carbonyl formation were significantly elevated in both livers and hearts after chronic ethanol consumption, with the cardiac lipid and protein damage being exaggerated by ADH transgene. CONCLUSION: These data suggest that increased cardiac acetaldehyde exposure due to ADH transgene may play an important role in cardiac contractile dysfunctions associated with lipid and protein damage after alcohol intake. SN - 0145-6008 UR - https://www.unboundmedicine.com/medline/citation/12878915/Cardiac_overexpression_of_alcohol_dehydrogenase_exacerbates_cardiac_contractile_dysfunction_lipid_peroxidation_and_protein_damage_after_chronic_ethanol_ingestion_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=2003&volume=27&issue=7&spage=1090 DB - PRIME DP - Unbound Medicine ER -