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Calcified Tissue International

, Volume 79, Issue 5, pp 326–339 | Cite as

Hypercholesterolemia Accelerates Vascular Calcification Induced by Excessive Vitamin D via Oxidative Stress

  • F. T. Tang
  • S. R. Chen
  • X. Q. Wu
  • T. Q. Wang
  • J. W. Chen
  • J. Li
  • L. P. Bao
  • H. Q. Huang
  • P. Q. LiuEmail author
Article

Abstract

Hypercholesterolemia plays an important role in the initiation and progression of atherosclerosis and has a positive correlation with cardiovascular disease. Calcification is a common feature of atherosclerotic lesions and contributes to cardiovascular dysfunctions. The present study investigated the role of hypercholesterolemia in vascular calcification and its potential mechanism. Models of vascular calcification were established by administering vitamin D2 (VD) to rats alone or combined with a high-cholesterol diet (HCD) and by treating rat aorta smooth muscle cells (RASMCs) with β-glycerophosphate (GP) alone or combined with oxidized low-density lipoprotein (oxLDL) in vitro. In rats, the combination of VD with HCD significantly enhanced vessel calcium deposition and the activity and mRNA expression of vessel alkaline phosphatase (ALP) compared to treatment with VD alone. This combination also enhanced serum levels of total cholesterol, oxLDL, and malondialdehyde as well as vascular production of superoxide anion, while it reduced the vascular activity of superoxide dismutase. Both simvastatin, a cholesterol-lowering agent, and antioxidant vitamin E antagonized the effects of the above combination. In RASMCs, oxLDL accumulation dependently accelerated calcium deposition in cell layers initiated by GP alone. Also, oxLDL stimulated ALP activity and mRNA expression in RASMCs in a concentration-dependent manner. Taken together, these results suggest that acceleration of vascular calcification by hypercholesterolemia might be attributed to oxidative stress and such calcification may be another target of statin or antioxidant action in antiatherosclerosis.

Keywords

Hypercholesterolemia Vascular calcification model Oxidized low-density lipoprotein Simvastatin Vitamin E 

Notes

Acknowledgment

This work was supported by the Major Program in Key Field of People’s Government of Guangdong Province, PR China (2003A30904); Key Program of the Ministry of Education, PR China (104146); Key Natural Science Fund of Guangdong Province, PR China (04105349); Key Program of Guangdong Province, PR China (2003B31713); and Key Program of Guangzhou City, PR China (2003Z1-E5011). We thank Ms. Liu Jie and Mr. Mo Mingcong for excellent technical support. We thank Professor Tao Liang for critical reading of the manuscript.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • F. T. Tang
    • 1
  • S. R. Chen
    • 1
  • X. Q. Wu
    • 1
  • T. Q. Wang
    • 1
  • J. W. Chen
    • 1
  • J. Li
    • 1
  • L. P. Bao
    • 1
  • H. Q. Huang
    • 1
  • P. Q. Liu
    • 1
    Email author
  1. 1.Laboratory of Pharmacology and Toxicology, School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouPeople’s Republic of China

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