Research Paper

Vitamin D Analogs Modulate the Expression of Plasminogen Activator Inhibitor-1, Thrombospondin-1 and Thrombomodulin in Human Aortic Smooth Muscle Cells
J. Ruth Wu-Wong, Masaki Nakane, Junli Ma

Abbott Laboratories, Abbott Park, Ill., USA

Address of Corresponding Author

J Vasc Res 2007;44:11-18 (DOI: 10.1159/000097812)

  Key Words

• Vitamin D receptor
• Cardiovascular disease
• Plasminogen activator inhibitor-1
• Thrombospondin-1
• Thrombomodulin

  Abstract

Background/Aims: Plasminogen activator inhibitor-1 (PAI-1), thrombospondin-1 (THBS1) and thrombomodulin (TM) are involved in atherothrombosis. Vitamin D receptor agonists (VDRAs) provide survival/cardiovascular benefits for chronic kidney disease patients. Methods: The effects of VDRAs on regulating PAI-1, THBS1 and TM in human aortic smooth muscle cells (SMC) and endothelial cells (EC) were studied. Results: In SMC, paricalcitol and calcitriol downregulated the expression of PAI-1 mRNA and protein in a dose-dependent manner (EC₅₀ = 0.7 and 4.4 nM, respectively). Both drugs also downregulated THBS1 mRNA and protein (EC₅₀ = 1.6 and 3.9 nM, respectively). In contrast, paricalcitol and calcitriol upregulated TM mRNA and protein (EC₅₀ = 28.9 and 25.5 nM, respectively). EC did not express VDR, and VDRAs failed to induce CYP24A1, a VDR target gene. The effect of paricalcitol on THBS1 in SMC was blocked by cycloheximide, while its effect on TM and CYP24A1 was not affected, suggesting that the regulation of THBS1 by VDR may be mediated through intermediate factors, but that TM is likely a direct target of VDR. Conclusion: VDR may play a role in atherothrombosis via regulation of PAI-1, THBS1 and TM.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. J. Ruth Wu-Wong
Abbott Laboratories, R46R, AP9
100 Abbott Park Rd.
Abbott Park, IL 60064 (USA)
Tel. +1 847 938 8492, Fax +1 847 936 1550, E-Mail ruth.r.wuwong@abbott.com

  Article Information

Received: July 15, 2006
Accepted after revision: September 28, 2006
Published online: December 7, 2006
Number of Print Pages : 8
Number of Figures : 4, Number of Tables : 1, Number of References : 37