Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice

Youchun Jiang, Corey Reynolds, Chang Xiao, Wenke Feng, Zhanxiang Zhou, Walter Rodriguez, Suresh C. Tyagi, John W. Eaton, Jack T. Saari, Yujian Kang

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Sustained pressure overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses preestablished hypertrophic cardiomyopathy caused by pressure overload induced by ascending aortic constriction in a mouse model. The reversal occurs in the continued presence of pressure overload. Sustained pressure overload leads to decreases in cardiac Cu and vascular endothelial growth factor (VEGF) levels along with suppression of myocardial angiogenesis. Cu supplementation replenishes cardiac Cu, increases VEGF, and promotes angiogenesis. Systemic administration of anti-VEGF antibody blunts Cu regression of hypertrophic cardiomyopathy. In cultured human cardiomyocytes, Cu chelation blocks insulin-like growth factor (IGF)-1- or Cu-stimulated VEGF expression, which is relieved by addition of excess Cu. Both IGF-1 and Cu activate hypoxia-inducible factor (HIF)-1α and HIF-1α gene silencing blocks IGF-1- or Cu-stimulated VEGF expression. HIF-1α coimmuno-precipitates with a Cu chaperone for superoxide dismutase-1 (CCS), and gene silencing of CCS, but not superoxide dismutase-1, prevents IGF-1- or Cu-induced HIF-1α activation and VEGF expression. Therefore, dietary Cu supplementation improves the condition of hypertrophic cardiomyopathy at least in part through CCS-mediated HIF-1α activation of VEGF expression and angiogenesis. JEM

Original languageEnglish (US)
Pages (from-to)657-666
Number of pages10
JournalJournal of Experimental Medicine
Volume204
Issue number3
DOIs
StatePublished - Mar 19 2007

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Hypertrophic Cardiomyopathy
Dietary Supplements
Hypoxia-Inducible Factor 1
Vascular Endothelial Growth Factor A
Copper
Pressure
Somatomedins
Superoxide Dismutase
Gene Silencing
Cardiomegaly
Cardiac Myocytes
Constriction
Heart Failure
Superoxide Dismutase-1
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. / Jiang, Youchun; Reynolds, Corey; Xiao, Chang; Feng, Wenke; Zhou, Zhanxiang; Rodriguez, Walter; Tyagi, Suresh C.; Eaton, John W.; Saari, Jack T.; Kang, Yujian.

In: Journal of Experimental Medicine, Vol. 204, No. 3, 19.03.2007, p. 657-666.

Research output: Contribution to journalArticle

Jiang, Y, Reynolds, C, Xiao, C, Feng, W, Zhou, Z, Rodriguez, W, Tyagi, SC, Eaton, JW, Saari, JT & Kang, Y 2007, 'Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice', Journal of Experimental Medicine, vol. 204, no. 3, pp. 657-666. https://doi.org/10.1084/jem.20061943
Jiang, Youchun ; Reynolds, Corey ; Xiao, Chang ; Feng, Wenke ; Zhou, Zhanxiang ; Rodriguez, Walter ; Tyagi, Suresh C. ; Eaton, John W. ; Saari, Jack T. ; Kang, Yujian. / Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 3. pp. 657-666.
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