Direct antiangiogenic actions of cadmium on human vascular endothelial cells

Direct antiangiogenic actions of cadmium on human vascular endothelial cells

The vascular endothelium is a primary target of cadmium (Cd) toxicity, but little is known regarding a potential mechanism whereby Cd may inhibit angiogenesis. Recent findings showing that Cd can disrupt cadherin-mediated cell–cell adhesion suggested that Cd might inhibit angiogenesis by altering th...

Full description

Saved in:
Bibliographic Details
Published in:Toxicology in vitro Vol. 22; no. 3; pp. 643 - 651
Main Authors: Woods, J.M., Leone, M., Klosowska, K., Lamar, P.C., Shaknovsky, T.J., Prozialeck, W.C.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-04-2008
Subjects:
Angiogenesis
Angiogenesis Inhibitors - pharmacology
Cadherins - metabolism
Cadmium
Cadmium - pharmacology
Cell Line
Cell Movement - drug effects
Cell Proliferation - drug effects
Cell Survival - drug effects
Chemotaxis - drug effects
Endothelial Cells - drug effects
Fluorescent Antibody Technique
Humans
Microtubules - ultrastructure
Myocytes, Smooth Muscle - drug effects
Cd
Cadmium
Angiogenesis
DMSO
HMVEC
PMA
FBS
HUVEC
EGM-2
EBM-2
EC
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The vascular endothelium is a primary target of cadmium (Cd) toxicity, but little is known regarding a potential mechanism whereby Cd may inhibit angiogenesis. Recent findings showing that Cd can disrupt cadherin-mediated cell–cell adhesion suggested that Cd might inhibit angiogenesis by altering the function of VE-cadherin, a molecule that is essential for angiogenesis. To address this issue, endothelial cells (ECs) were exposed to Cd in the presence of serum and subjected to angiogenesis-related cell migration and tube formation assays. Initial examination of cytotoxicity showed that ECs are rather resistant to the acute cytotoxic effects of Cd even at concentrations up to 1mM. However, 10μM Cd decreased migration of ECs. Cd concentrations of 500nM and greater significantly reduced organization of microvascular ECs into tubes. These antiangiogenic effects were evident even when ECs were preincubated with Cd and then washed to remove free Cd, indicating that Cd acted directly on the cells rather than on the extracellular matrix. Immunolocalization studies showed that Cd caused the redistribution of VE-cadherin from cell to cell contacts. These findings indicate that Cd acts in an angiostatic manner on ECs, and that this effect may involve alterations in the localization and function of VE-cadherin.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2007.12.009