Alcohol-Induced Myocardial Fibrosis in Metallothionein-Null Mice: Prevention by Zinc Supplementation  [2005]

Wang, Lipeng Zhou, Zhanxiang Saari, Jack T. Kang, Y. James

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Alcohol-induced cardiomyopathy including fibrosis has been recognized clinically for a long time, but its pathogenesis is incompletely understood. Studies using experimental animals have not fully duplicated the pathological changes in humans, and animal models of alcoholic cardiac fibrosis are not available. In the present study, we have developed a mouse model in which cardiac hypertrophy and fibrosis were produced in metallothionein-knockout (MT-KO) mice fed an alcohol-containing liquid diet for 2 months. The same alcohol feeding did not produce cardiac fibrosis in the wild-type (WT) control mice, although there was no difference in the alcohol-induced heart hypertrophy between the WT controls and the MT-KO mice. Zinc supplementation prevented cardiac fibrosis but did not affect heart hypertrophy in the alcohol-fed MT-KO mice, suggesting a specific link between zinc homeostasis and cardiac fibrosis. Serum creatine phosphokinase activity was significantly higher in the alcohol-administered MT-KO mice than in the WT mice, and zinc supplementation decreased serum creatine phosphokinase activities and eliminated the difference between the groups. Thus, disturbance in zinc homeostasis due to the lack of MT associates with alcohol-induced cardiac fibrosis and more severe cardiac injury, making the MT-KO mouse model of alcohol-induced cardiac fibrosis a useful tool to investigate specific factors involved in the alcoholic cardiomyopathy.

Other subjects

  • animal models
  • knockout mutants
  • alcohol abuse
  • alcoholic cardiomyopathy
  • myocardium
  • metallothionein
  • mice
  • ethanol
  • mineral metabolism
  • protective effect
  • heart diseases
  • dietary mineral supplements
  • fibrosis
  • cardiomyopathy
  • cardioprotective effect
  • zinc

From the journal

American journal of pathology

ISSN : 1525-2191

Other information

Language : English

Type : Journal Article

In AGRIS since : 2013

Volume : 167

Issue : 2

Start Page : 337

End Page : 344

All titles :

" Alcohol-Induced Myocardial Fibrosis in Metallothionein-Null Mice: Prevention by Zinc Supplementation "