Copper stimulates growth of human umbilical vein endothelial cells in a vascular endothelial growth factor-independent pathway

Shun Li, Huiqi Xie, Shengfu Li, Yujian Kang

Research output: Contribution to journalArticle

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Abstract

Studies in vivo have shown that dietary copper (Cu) supplementation reverses pressure overload-induced cardiac hypertrophy in a mouse model, which is vascular endothelial growth factor (VEGF)-dependent and correlates with enhanced angiogenesis. Because Cu stimulation of endothelial cell growth and differentiation would play a critical role in angiogenesis, the present study was undertaken to examine the effect of Cu on growth of human umbilical vein endothelial cells (HUVECs) in cultures. The HUVECs were treated with CuSO4 at a final concentration of 5 μmol/L Cu element in cultures or with a Cu chelator, tetraethylenepentamine (TEPA), at a final concentration of 25 μmol/L in cultures. Cell growth and Cu effect on cell cycle were determined. In addition, the effect of Cu on VEGF and endothelial nitric oxide synthase (eNOS) mRNA levels was determined, and anti-VEGF antibody and siRNA targeting eNOS were applied to determine the role of VEGF or eNOS in the Cu effect on cell growth. Cu significantly stimulated and TEPA significantly inhibited cell growth, and the TEPA effect was blocked by excess Cu. Cu increased the number of cells in the S phase and correspondingly decreased the number in the G1 phase. Interestingly, Cu did not increase the level of VEGF mRNA, but significantly increased eNOS mRNA. Furthermore, neutralizing VEGF by anti-VEGF antibody did not suppress Cu stimulation of cell growth. However, siRNA targeting eNOS completely blocked Cu reversal of TEPA inhibition of cell growth. The data demonstrate that Cu stimulation of HUVEC cell growth is VEGF-independent, but eNOS-dependent.

Original languageEnglish (US)
Pages (from-to)77-82
Number of pages6
JournalExperimental Biology and Medicine
Volume237
Issue number1
DOIs
StatePublished - Jan 1 2012

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Endothelial cells
Human Umbilical Vein Endothelial Cells
Cell growth
Vascular Endothelial Growth Factor A
Nitric Oxide Synthase Type III
Copper
Growth
Cell culture
Messenger RNA
Small Interfering RNA
Antibodies
G1 Phase
Cardiomegaly
Chelating Agents
S Phase
Cell Differentiation
Cell Cycle
Endothelial Cells
Cell Culture Techniques
Cell Count

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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Copper stimulates growth of human umbilical vein endothelial cells in a vascular endothelial growth factor-independent pathway. / Li, Shun; Xie, Huiqi; Li, Shengfu; Kang, Yujian.

In: Experimental Biology and Medicine, Vol. 237, No. 1, 01.01.2012, p. 77-82.

Research output: Contribution to journalArticle

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