doi: 10.1161/01.RES.0000149165.99974.12
© 2004 American Heart Association, Inc.
Review |
Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin
From the Department of Biology and Division of Bone and Mineral Research, Washington University, St Louis, Mo.
Correspondence to Patricia Collin-Osdoby, PhD, Biology, Box 1229 Washington University St Louis, MO 63130. E-mail collin{at}biology.wustl.edu
This Review is part of a thematic series on Mechanisms of Vascular Calcification, which includes the following articles:
Pathophysiology of Vascular Calcification in Chronic Kidney Disease
Mesenchymal Stem Cells and the Artery Wall
Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin
Angiogenesis and Pericytes in Initiation of Ectopic Calcification
Osteopontin Promoter Regulation and Phosphate Transport Molecules in Vascular Calcification
Role of Bone Morphogenetic Proteins in Vascular Calcification
Linda Demer Guest Editor
Vascular calcification often occurs with advancing age, atherosclerosis, various metabolic disorders such as diabetes mellitus and end-stage renal disease, or in rare genetic diseases, leading to serious clinical consequences. Such mineralization can occur at various sites (cardiac valves, arterial intima or media, capillaries), involve localized or diffuse widespread calcification, and result from numerous causes that provoke active inflammatory and osteogenic processes or disordered mineral homeostasis. Although valuable research has defined many key factors and cell types involved, surprising new insights continue to arise that deepen our understanding and suggest novel research directions or strategies for clinical intervention in calcific vasculopathies. One emerging area in vascular biology involves the RANKL/RANK/OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of immune and skeletal biology. Evidence is accumulating that such signals may be expressed, regulated, and function in vascular physiology and pathology in unique ways to promote endothelial cell survival, angiogenesis, monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and calcification. Concerted research efforts are greatly needed to understand these potential roles, clarify whether RANKL (receptor activator of nuclear factor 
B ligand) promotes and osteoprotegerin (OPG) protects against vascular calcification, define how OPG genetic polymorphisms relate to cardiovascular disease, and learn whether elevated serum OPG levels reflect endothelial dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important and complex links between the vascular, skeletal, and immune systems. Thus, these molecules may play a central role in regulating the development of vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease.
Key Words: RANKL • OPG • calcification • artherosclerosis • blood vessels
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