Copper reverses cardiomyocyte hypertrophy through vascular endothelial growth factor-mediated reduction in the cell size

Yang Zhou, Youchun Jiang, Yujian Kang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)106-117
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume45
Issue number1
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

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Cell Size
Cardiac Myocytes
Hypertrophy
Vascular Endothelial Growth Factor A
Copper
Cardiomegaly
Phenylephrine
Copper Sulfate
Ventricular Myosins
Myosin Heavy Chains
In Situ Nick-End Labeling
Atrial Natriuretic Factor
Dietary Supplements
Cell Division
Histones
Actins
Cell Cycle
Flow Cytometry
Proteins
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Copper reverses cardiomyocyte hypertrophy through vascular endothelial growth factor-mediated reduction in the cell size. / Zhou, Yang; Jiang, Youchun; Kang, Yujian.

In: Journal of Molecular and Cellular Cardiology, Vol. 45, No. 1, 01.07.2008, p. 106-117.

Research output: Contribution to journalArticle

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