Long-term zinc deprivation accelerates rat vascular smooth muscle cell proliferation involving the down-regulation of JNK1/2 expression in MAPK signaling

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• 作者：Ethel H. Alcantara^a ; ^{ethel_chem420@yahoo.com} ; Mee Young Shin^a ; ^{shinmy09@hanmail.net} ; Jö ; rg Feldmann^b ; ^{j.feldmann@abdn.ac.uk} ; Graeme F. Nixon^c ; ^{g.f.nixon@abdn.ac.uk} ; John H. Beattie^d ; ^{j.beattie@abdn.ac.uk} ; In Sook Kwun^a ; ^{iskwun@andong.ac.kr}
• 关键词：Atherosclerosis ; Vascular smooth muscle cell (VSMC) ; A7r5 ; VSMC proliferation ; Zinc ; MAPK-JNK1/2
• 刊名：Atherosclerosis
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：228
• 期：1
• 页码：46-52
• 全文大小：971 K

文摘

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?¦ÌM Zn) for short- (¡Ü12?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?¦ÌM 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?¦ÌM) 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.