Copper reverses cardiomyocyte hypertrophy through vascular endothelial growth factor-mediated reduction in the cell size
| Autor: | Y. James Kang, Youchun Jiang, Yang Zhou |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Cardiotonic Agents Copper Sulfate Time Factors Cell division Antidotes Cell Apoptosis Cardiomegaly Biology Article Muscle hypertrophy Rats Sprague-Dawley Mice Phenylephrine chemistry.chemical_compound Atrial natriuretic peptide Internal medicine medicine Animals Myocytes Cardiac Molecular Biology Cells Cultured Cell Size Pressure overload TUNEL assay Dose-Response Relationship Drug Rats Vascular endothelial growth factor medicine.anatomical_structure Endocrinology chemistry Cardiology and Cardiovascular Medicine Biomarkers |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 45:106-117 |
| ISSN: | 0022-2828 |
| Popis: | Previous studies have shown that dietary copper supplementation reversed heart hypertrophy induced by pressure overload in a mouse model. The present study was undertaken to understand the cellular basis of copper-induced regression of cardiac hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylephrine (PE) at a final concentration of 100 μM in cultures for 48 h to induce cellular hypertrophy. The hypertrophied cardiomyocytes were exposed to copper sulfate at a final concentration of 5 μM in cultures for additional 24 h. This copper treatment reduced the size of the hypertrophied cardiomyocytes, as measured by flow cytometry, protein content in cells, cell volume and cardiomyocyte hypertrophy markers including beta-myosin heavy chain protein, skeletal alpha-actin, and atrial natriuretic peptide. Cell cycle analysis and cell sorting of p -histone-3 labeled cardiomyocytes indicated that cell division was not involved in the copper-induced regression of cardiomyocyte hypertrophy. Copper also inhibited PE-induced apoptosis, determined by a TUNEL assay. Because copper stimulates vascular endothelial growth factor (VEGF) production through activation of hypoxia-inducible transcription factor, an anti-VEGF antibody at a final concentration of 2 ng/ml in cultures was used and shown to blunt copper-induced regression of cell hypertrophy. Conversely, VEGF alone at a final concentration of 0.2 μg/ml reversed cell hypertrophy as the same as copper did. This study demonstrates that both copper and VEGF reduce the size of hypertrophied cardiomyocytes, and copper regression of cardiac hypertrophy is VEGF-dependent. |
| Databáze: | OpenAIRE |
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