Alcohol-induced myocardial fibrosis in metallothionein-null mice

Prevention by zinc supplementation

Lipeng Wang, Zhanxiang Zhou, Jack T. Saari, Yujian Kang

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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 hi 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.

Original languageEnglish (US)
Pages (from-to)337-344
Number of pages8
JournalAmerican Journal of Pathology
Volume167
Issue number2
DOIs
StatePublished - Jan 1 2005

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Metallothionein
Zinc
Fibrosis
Alcohols
Knockout Mice
Cardiomegaly
Creatine Kinase
Homeostasis
Alcoholic Cardiomyopathy
Serum
Cardiomyopathies
Animal Models
Diet
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Alcohol-induced myocardial fibrosis in metallothionein-null mice : Prevention by zinc supplementation. / Wang, Lipeng; Zhou, Zhanxiang; Saari, Jack T.; Kang, Yujian.

In: American Journal of Pathology, Vol. 167, No. 2, 01.01.2005, p. 337-344.

Research output: Contribution to journalArticle

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