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Phosphate-Induced Rat Vascular Smooth Muscle Cell Calcification and the Implication of Zinc Deficiency in A7r5 Cell Viability

  • Shin, Mee-Young (Department of Food Science and Nutrition, Andong National University) ;
  • Kwun, In-Sook (Department of Food Science and Nutrition, Andong National University)
  • Received : 2013.06.13
  • Accepted : 2013.06.19
  • Published : 2013.06.30

Abstract

The calcification of vascular smooth muscle cells (VSMCs) is considered one of the major contributors for vascular disease. Phosphate is known as the inducer for VSMC calcification. In this study, we assessed whether phosphate affected cell viability and fetuin-A, a calcification inhibitor protein, both which are related to VSMC calcification. Also, VSMC viability by zinc level was assessed. The results showed that phosphate increased Ca and P deposition in VSMCs (A7r5 cell line, rat aorta origin). This phosphate-induced Ca and P deposition was consistent with the decreased A7r5 cell viability (P<0.05), which implies phosphate-induced calcification in A7r5 cells might be due to the decreased VSMC cell viability. As phosphate increased, the protein expression of fetuin-A protein was up-regulated. A7r5 cell viability decreased as the addition of cellular zinc level was decreased (P<0.05). The results suggested that zinc deficiency causes the decreased cell viability and it would be the future study to clarify how zinc does act for VSMC cell viability. The results suggest that the decreased VSMC viability by high P or low Zn in VSMCs may be the risk factor for vascular disease.

Keywords

References

  1. Shroff RC, Shanahan CM. 2007. The vascular biology of calcification. Semin Dial 20: 103-109. https://doi.org/10.1111/j.1525-139X.2007.00255.x
  2. Giachelli CM. 2009. The emerging role of phosphate in vascular calcification. Kidney Int 75: 890-897. https://doi.org/10.1038/ki.2008.644
  3. Speer MY, Giachelli CM. 2004. Regulation of cardiovascular calcification. Cardiovasc Pathol 13: 63-70.
  4. Trion A, van der Laarse A. 2004. Vascular smooth muscle cells and calcification in atherosclerosis. Am Heart J 147: 808-814. https://doi.org/10.1016/j.ahj.2003.10.047
  5. Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM. 2000. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87: E10-E17. https://doi.org/10.1161/01.RES.87.7.e10
  6. Son BK, Akishita M, Iijima K, Eto M, Ouchi Y. 2008. Mechanism of pi-induced vascular calcification. J Atheroscler Thromb 15: 63-68. https://doi.org/10.5551/jat.E545
  7. Giachelli CM, Speer MY, Li X, Rajachar RM, Yang H. 2005. Regulation of vascular calcification: roles of phosphate and osteopontin. Circ Res 96: 717-722. https://doi.org/10.1161/01.RES.0000161997.24797.c0
  8. Alcantara EH, Shin MY, Feldmann J, Nixon GF, Beattie JH. Kwun IS. 2013. Long-term zinc deprivation accelerates rat vascular smooth muscle cell proliferation involving the down-regulation of JNK1/2 expression in MAPK signaling. Atherosclerosis 228: 46-52. https://doi.org/10.1016/j.atherosclerosis.2013.01.030
  9. Li X, Yang HY, Giachelli CM. 2006. Role of the sodiumdependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification. Circ Res 98: 905-912. https://doi.org/10.1161/01.RES.0000216409.20863.e7
  10. Li X, Giachelli CM. 2007. Sodium-dependent phosphate cotransporters and vascular calcification. Curr Opin Nephrol Hypertens 16: 325-328. https://doi.org/10.1097/MNH.0b013e3281c55ef1
  11. Giachelli CM, Jono S, Shioi A, Nishizawa Y, Mori K, Morii H. 2001. Vascular calcification and inorganic phosphate. Am J Kidney Dis 38: S34-S37.
  12. Giachelli CM. 2003. Vascular calcification: in vitro evidence for the role of inorganic phosphate. J Am Soc Nephrol 14: S300-S304. https://doi.org/10.1097/01.ASN.0000081663.52165.66
  13. Ou O, Allen-Redpath K, Urgast D, Gordon MJ, Campbell G, Feldmann J, Nixon GF, Mayer CD, Kwun IS, Beattie JH. 2013. Plasma zinc's alter ego is a low-molecular-weight humoral factor. FASEB J 27: doi: 10.1096/fj.13-228791
  14. Allen-Redpath K, Ou O, Beattie JH, Kwun IS, Feldmann J, Nixon GF. 2013. Marginal dietary zinc deficiency in vivo induces vascular smooth muscle cell apoptosis in large arteries. Cardiovasc Res 99: doi: 10.1093/cvr/cvt114
  15. Reynolds JL, Skepper JN, McNair R, Kasama T, Gupta K, Weissberg PL, Jahnen-Dechent W, Shanahan CM. 2005. Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol 16: 2920-2930. https://doi.org/10.1681/ASN.2004100895
  16. Chen NX, O'Neill KD, Chen X, Duan D, Wang E, Sturek MS, Edwards JM, Moe SM. 2007. Fetuin-A uptake in bovine vascular smooth muscle cells is calcium dependent and mediated by annexins. Am J Physiol Renal Physiol 292: F599- F606. https://doi.org/10.1152/ajprenal.00303.2006
  17. Jahnen-Dechent W, Heiss A, Schafer C, Ketteler M. 2011. Fetuin-A regulation of calcified matrix metabolism. Circ Res 108: 1494-1509. https://doi.org/10.1161/CIRCRESAHA.110.234260
  18. Heiss A, DuChesne A, Denecke B, Grotzinger J, Yamamoto K, Renne T, Jahnen-Dechent W. 2003. Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 278: 13333-13341. https://doi.org/10.1074/jbc.M210868200

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