Osteoprotegerin Inhibits Vascular Calcification Without Affecting Atherosclerosis in Ldlr(-/-) Mice

Overview

Journal Circulation

Specialty Cardiology & Vascular Diseases

Date 2008 Jan 4

PMID 18172035

Citations 105

Authors

Sean Morony

Yin Tintut

Zina Zhang

Russell C Cattley

Gwyneth Van

Denise Dwyer

Marina Stolina

Paul J Kostenuik

Linda L Demer

Affiliations

Soon will be listed here.

Abstract

Background: The role of osteoprotegerin in vascular disease is unclear. Recent observational studies show that serum osteoprotegerin levels are associated with the severity and progression of coronary artery disease, atherosclerosis, and vascular calcification in patients. However, genetic and treatment studies in mice suggest that osteoprotegerin may protect against vascular calcification.

Methods And Results: To test whether osteoprotegerin induces or prevents vascular disease, we treated atherogenic diet-fed ldlr(-/-) mice with recombinant osteoprotegerin (Fc-OPG) or vehicle for 5 months. Vehicle-treated mice developed significant, progressive atherosclerosis with increased plasma osteoprotegerin levels, consistent with observational studies, and approximately 15% of these atherosclerotic lesions developed calcified cartilage-like metaplasia. Treatment with Fc-OPG significantly reduced the calcified lesion area without affecting atherosclerotic lesion size or number, vascular cytokines, or plasma cholesterol levels. Treatment also significantly reduced tissue levels of aortic osteocalcin, a marker of mineralization.

Conclusions: These data support a role for osteoprotegerin in the vasculature as an inhibitor of calcification and a marker, rather than a mediator, of atherosclerosis.

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