Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice
| Autor: | Jack T. Saari, Suresh C. Tyagi, Walter E. Rodriguez, Zhanxiang Zhou, Chang Xiao, Youchun Jiang, Wenke Feng, Corey L. Reynolds, Y. James Kang, John W. Eaton |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Angiogenesis medicine.medical_treatment Immunology Cardiomyopathy 030204 cardiovascular system & hematology Biology Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Humans Immunology and Allergy Cells Cultured 030304 developmental biology Pressure overload 0303 health sciences Superoxide Growth factor Hypertrophic cardiomyopathy Articles Cardiomyopathy Hypertrophic medicine.disease Mice Inbred C57BL Vascular endothelial growth factor Disease Models Animal Endocrinology chemistry Heart failure Chronic Disease Dietary Supplements Hypertension Copper |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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)-1alpha and HIF-1alpha gene silencing blocks IGF-1- or Cu-stimulated VEGF expression. HIF-1alpha coimmunoprecipitates 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-1alpha activation and VEGF expression. Therefore, dietary Cu supplementation improves the condition of hypertrophic cardiomyopathy at least in part through CCS-mediated HIF-1alpha activation of VEGF expression and angiogenesis. |
| Databáze: | OpenAIRE |
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