doi: 10.1161/01.RES.00000175571.53833.6c
© 2005 American Heart Association, Inc.
Review |
Bone Morphogenetic Proteins in Vascular Calcification
From the Renal Division, Departments of Pediatrics (K.A.H., S.M.) and Internal Medicine (K.A.H., G.S.), Washington University School of Medicine, St. Louis, Mo.
Correspondence to Dr Keith A. Hruska, Department of Pediatrics, Campus Box 8208, 5th Floor McDonnell Pediatric Research Building, 660 S Euclid, St. Louis, MO 63110. E-mail hruska_k{at}kids.wustl.edu
This Review is part of a thematic series on Mechanisms of Vascular Calcification, which includes the following articles:
The 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 OPG
Regulation of Vascular Calcification: Roles of Phosphate and Osteopontin
Angiogenesis and Pericytes in the Initiation of Ectopic Calcification
Bone Morphogenetic Proteins in Vascular Calcification
Linda Demer Guest Editor
Vascular calcification is a common problem among the elderly and those with chronic kidney disease (CKD) and diabetes. The process of tunica media vascular calcification in CKD appears to involve a phenotypic change in the vascular smooth muscle cell (VSMC) resulting in cell-mediated mineralization of the extracellular matrix. The bone morphogenetic proteins (BMPs) are important regulators in orthotopic bone formation, and their localization at sites of vascular calcification raises the question of their role. In this review, we will discuss the actions of the BMPs in vascular calcification. Although the role of BMP-2 in vascular calcification is not proven, it has been the most studied member of the BMP family in this disease process. The role of BMP-2 may be through inducing osteoblastic differentiation of VSMCs through induction of MSX-2, or by inducing apoptosis of VSMCs, a process thought critical in the initiation of vascular calcification. Additionally, BMP-2 may be related to loss of regulation of the matrix Gla protein. A second BMP, BMP-7, less studied than BMP-2 may have opposing actions in vascular calcification. In postnatal life, BMP-7 is expressed primarily in the kidney, and expression is diminished by renal injury. BMP-7 is an important regulator of skeletal remodeling and the VSMC phenotype. BMP-7 restores skeletal anabolic balance in animal models of CKD with disordered skeletal modeling, also reducing serum phosphate in the process. BMP-7 also reverses vascular calcification in CKD, and reduction in vascular calcification is due, in part, to reduced serum phosphate, an important inducer of VSMC-mediated vascular mineralization and in part to direct actions on the VSMC.
Key Words: bone morphogenetic proteins • vascular calcification • chronic kidney disease • vascular smooth muscle cells • Smad6 • MSX-2
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