Research Paper

Human Full-Length Osteoprotegerin Induces the Proliferation of Rodent Vascular Smooth Muscle Cells both in vitro and in vivo
Riccardo Candido^a, Barbara Toffoli^d, Federica Corallini^b, Stella Bernardi^c, Davide Zella^e, Rebecca Voltan^c, Vittorio Grill^b, Claudio Celeghini^b, Bruno Fabris<sup>c

a</sup>Diabetic Center, ASS 1 Triestina,
^bDepartment of Biomedicine,
^cInterdepartmental Center of Molecular Medicine, University of Trieste, Trieste, and
^dDepartment of Morphology and Embryology, University of Ferrara, Ferrara, Italy;
^eInstitute of Human Virology - School of Medicine, University of Maryland, Baltimore, Md., USA

Address of Corresponding Author

J Vasc Res 2010;47:252-261 (DOI: 10.1159/000257339)

  Key Words

• Osteoprotegerin
• Vascular smooth muscle cells
• Apolipoprotein E-null mice
• Cell proliferation
• Atherosclerosis

  Abstract

Background/Aims: Since elevated plasma levels of osteoprotegerin (OPG) represent a risk factor for death and heart failure in patients affected by diabetes mellitus and coronary artery disease, this study aimed to elucidate potential roles of OPG in the pathogenesis of atherosclerosis. Methods and Results: Recombinant human full-length OPG, used at concentrations comparable to the elevated levels found in the serum of diabetic patients, significantly increased the proliferation rate of rodent vascular smooth muscle cells (VSMC). To mimic the moderate chronic elevation of OPG observed in diabetic patients, low doses (1 µg/mouse) of full-length human OPG were injected intraperitoneally every 3 weeks in diabetic apolipoprotein E (apoE)-null mice. The group of animals treated for 12 weeks with recombinant OPG showed a small increase in the total aortic plaque area at necropsy in comparison to vehicle-treated animals. Importantly, while no differences in the amount of interstitial collagen or the degree of macrophage infiltration were observed between OPG-treated and vehicle-treated apoE-null diabetic animals, a significant increase in the number of -actin-positive smooth muscle cells was observed in the plaques of OPG-treated mice. Conclusions: Our data suggest that OPG promotes VSMC proliferation and might be directly involved in pathogenetic aspects of atherosclerosis.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Dr. Claudio Celeghini
Department of Biomedicine, University of Trieste
Via Manzoni 16
IT-34100 Trieste (Italy)
Tel. +39 040 558 6000, Fax +39 040 558 6018, E-Mail cceleghini@units.it

  Article Information

Received: January 2, 2009
Accepted after revision: June 8, 2009
Published online: November 11, 2009
Number of Print Pages : 10
Number of Figures : 6, Number of Tables : 1, Number of References : 47