title: Long-term zinc deprivation accelerates rat vascular smooth muscle cell proliferation involving the down-regulation of JNK1/2 expression in MAPK signaling.
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.
  
  
  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 r(2) = -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.
  
  
  CONCLUSIONS
  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.
authors: Department of Food Science and Nutrition, Andong National University, 388 Songchundong, Andong, Kyungbook 760-749, South Korea. ethel_chem420@yahoo.com
authors: Ethel H
authors: EH
authors: Alcantara
authors: Mee Young
authors: MY
authors: Shin
authors: Jörg
authors: J
authors: Feldmann
authors: Graeme F
authors: GF
authors: Nixon
authors: John H
authors: JH
authors: Beattie
authors: In Sook
authors: IS
authors: Kwun
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003470:Culture Media / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D015032:Zinc / Q000172:deficiency* / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D015032:Zinc; D002118:Calcium