Abstract
Background
The accelerated proliferation of vascular smooth muscle cells (VSMCs) is a contributor
for atherosclerosis by thickening the vascular wall. Since zinc modulation of VSMC
proliferation has not been clarified, this study investigated whether zinc affects
VSMC proliferation.
Methods and results
Both a rat aorta origin vascular smooth muscle cell line (A7r5 VSMCs) and primary
VSMCs which were collected from rat aorta (pVSMCs) were cultured with zinc (0–50 μM
Zn) for short- (≤12 d) and long-term (28 d) periods under normal non-calcifying (0
or 1 mM P) or calcifying (>2 mM P) P conditions. Mouse vascular endothelial cells
(MS I cells) were also cultured (under 0–50 μM Zn and 10 mM P for 20 d) to compare
with VSMC cultures. While during short-term culture of VSMCs, zinc deprivation decreased
cell proliferation in a zinc-concentration manner both under non-calcifying and calcifying
conditions in A7r5 and pVSMCs (P < 0.05), during long-term cultures (28 d), A7r5 VSMC proliferation was inversely
related to medium zinc concentration under normal physiological P conditions (regression
coefficient r2 = −0.563, P = 0.012). The anti-cell proliferative effect of zinc supplementation (>50 μM) was
VSMC-specific. Long-term (35 d), low zinc treatment down-regulated JNK expression
and activation, while not affecting ERK1/2 MAPK signaling in A7r5 VSMCs.
Conclusion
The results showed that chronic zinc deprivation accelerated VSMC proliferation, perhaps
due to down-regulation of MAPK-JNK signaling, and that the anti-cell proliferative
role of zinc is VSMC-specific. The findings suggested that zinc may have anti-VSMC
proliferative properties in atherosclerosis.
Highlights
- Chronic (long-term) Zn deprivation accelerated VSMC proliferation.
- Zn deprivation-induced VSMC proliferation was associated with decreased JNK levels.
- Anti-proliferative effect of Zn was found to be VSMC-specific.
Keywords
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Article info
Publication history
Published online: March 06, 2013
Accepted:
January 25,
2013
Received in revised form:
December 30,
2012
Received:
August 1,
2012
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
