Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldlr(-/-) mice.
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.


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.
Morony
Sean
S
Department of Molecular Cellular and Integrative Physiology, University of California, Los Angeles, USA.
Tintut
Yin
Y
Zhang
Zina
Z
Cattley
Russell C
RC
Van
Gwyneth
G
Dwyer
Denise
D
Stolina
Marina
M
Kostenuik
Paul J
PJ
Demer
Linda L
LL
D000818:Animals; D001011:Aorta; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology*; D002114:Calcinosis / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D053244:Osteoprotegerin / Q000097:blood / Q000494:pharmacology*; D053245:RANK Ligand / Q000097:blood; D012333:RNA, Messenger / Q000097:blood; D011973:Receptors, LDL / Q000172:deficiency; D011994:Recombinant Proteins; D014652:Vascular Diseases / Q000209:etiology / Q000473:pathology*
D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D011973:Receptors, LDL; D011994:Recombinant Proteins