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intracellular labile iron induced monocyte adhesion to endothelium, an initial
event in atherosclerotic plaque formation
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2257.)
© 2004 American Heart Association, Inc.
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Vascular Biology
Intracellular Labile Iron Modulates Adhesion of Human Monocytes to Human
Endothelial Cells
Apriliana E.R. Kartikasari; Niki A. Georgiou; Frank L.J. Visseren; Henny van
Kats-Renaud; B. Sweder van Asbeck; Joannes J.M. Marx
From the Eijkman-Winkler Center for Medical Microbiology (A.E.R.K., N.A.G.,
F.L.J.V., H.v.K.-R., B.S.v.A., J.J.M.M.), Infectious Diseases, and Inflammation
and Eijkman Graduate School for Immunology and Infectious Diseases, and the
Departments of Vascular Medicine (F.L.J.V.) and Internal Medicine (B.S.v.A.),
University Medical Center Utrecht, The Netherlands.
Correspondence Prof Joannes J.M. Marx, MD, PhD, Eijkman-Winkler Center for
Medical Microbiology, Infectious Diseases, and Inflammation, university Medical
Center Utrecht, 100 Heidelberglaan G04.614, 3584CX Utrecht, The Netherlands.
Email jmarx@azu.nl
Objective— Elevated iron stores and high plasma iron concentration have been
linked to an increased risk of atherosclerosis. Iron may thereby affect the
interaction of monocytes to endothelium, an initial event in the formation of
atherosclerotic plaques.
Methods and Results— Addition of 10 µmol/L non–transferrin-bound iron to
the incubation medium caused a 2-fold increase in monocyte adhesion to human
umbilical vein endothelial cells (HUVECs). A concordant increase in the
expression of the following adhesion molecules was observed: vascular cell
adhesion molecule-1, intercellular adhesion molecule-1, and endothelial
selectin on HUVECs as well as very late antigen-4, and lymphocyte
function–associated antigen-1 on monocytes. The inclusion of either
deferiprone or salicylaldehyde isonicotinoylhydrazone counteracted these
effects. Intracellular iron chelation by deferoxamine was completed only after
10 hours of incubation, shown by reversal of iron-quenched intracellular
calcein signal, and concurrently the effects of iron were blunted. The
membrane-impermeable chelator, diethylenetriamine pentaaceticacid, failed to
negate iron effects, even after 48 hours of treatment. Furthermore, only
membrane-permeable superoxide or hydroxyl radical scavengers were capable of
preventing HUVEC activation by iron.
Conclusions— Non–transferrin-bound iron increases the level of
intracellular labile iron, which promotes monocyte recruitment to endothelium
and may thereby contribute to the pathogenesis of atherosclerosis. Iron-induced
adhesion molecule expression was observed, and this event may involve the
production of oxygen radicals.
An increase in the level of intracellular labile iron induced monocyte adhesion
to endothelium, an initial event in atherosclerotic plaque formation. A
concordant increase in the cell adhesion molecule expression was observed.
Furthermore, only inclusion of membrane-permeable iron chelators and radical
scavengers resulted in a complete inhibition of these effects of iron.
Key Words: iron • atherosclerosis • monocytes • endothelium • adhesion
molecules
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Copyright © 2004 by the American Heart Association.
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