doi: 10.1161/01.RES.0000141775.67189.98
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© 2004 American Heart Association, Inc.
Reviews |
Pathophysiology of Vascular Calcification in Chronic Kidney Disease
From the Indiana University School of Medicine (S.M.M., N.X.C.) and Roudebush Veterans Affairs Medical Center (S.M.M.), Indianapolis, Ind.
Correspondence to Sharon M. Moe, MD, Indiana University School of Medicine, Wishard Memorial Hospital, 1001 W 10th St, OPW 526 Indianapolis, IN 46202. E-mail smoe{at}iupui.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
Angiogenesis and Pericytes in Initiation of Ectopic Calcification
Lineage Diversity of Vascular Stem Cells: Bone, Cartilage, Marrow
Osteopontin Promoter Regulation and Phosphate Transport Molecules in Vascular Calcification
Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin
Role of Bone Morphogenetic Proteins in Vascular Calcification
Linda Demer Guest Editor
Patients with chronic kidney disease (CKD) on dialysis have 2- to 5-fold more coronary artery calcification than age-matched individuals with angiographically proven coronary artery disease. In addition to increased traditional risk factors, CKD patients also have a number of nontraditional cardiovascular risk factors that may play a prominent role in the pathogenesis of arterial calcification, including duration of dialysis and disorders of mineral metabolism. In histological specimens from the inferior epigastric artery of dialysis patients, we have found expression of the osteoblast differentiation factor core binding factor 
-1 (Cbfa1) and several bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) in both the intima and medial layers when calcification was present. In cultured vascular smooth muscle cells, the addition of pooled serum from dialysis patients (versus normal healthy controls) accelerated mineralization and increased expression of Cbfa1, osteopontin, and alkaline phosphatase to a similar magnitude as does ß-glycerophosphate alone. However, a lack of inhibitors of calcification may also be important. Dialysis patients with low levels of serum fetuin-A, a circulating inhibitor of mineralization, have increased coronary artery calcification and fetuin-A can inhibit mineralization of vascular smooth muscle cells in vitro. These data support that elevated levels of phosphorus and/or other potential uremic toxins may play an important role by transforming vascular smooth muscle cells into osteoblast-like cells, which can produce a matrix of bone collagen and noncollagenous proteins. This nidus can then mineralize if the balance of pro-mineralizing factors outweighs inhibitory factors.
Key Words: vascular calcification • chronic kidney disease • dialysis • core binding factor -1
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