Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels.
BACKGROUND
Bone matrix proteins are expressed in calcified arteries from dialysis patients, suggesting that vascular smooth muscle cells (VSMCs) may transform to osteoblast-like cells. One of the key transcriptional regulators of osteoblast differentiation is Cbfa1. Thus, we hypothesized that this may be a key factor in arterial calcification.


METHODS
To test this hypothesis, we examined sections of the inferior epigastric artery from uremic patients for the presence of Cbfa1 and type I collagen and osteopontin by in situ hybridization and immunostaining. We also examined the effect of pooled uremic sera from dialysis patients on the expression of Cbfa1 by reverse transcription-polymerase chain reaction (RT-PCR) in bovine VSMCs in vitro.


RESULTS
Cbfa1 and osteopontin were expressed in both the media and the intima in vessels that were calcified, but there was only minimal staining in non-calcified vessels. In vitro studies demonstrated that pooled uremic serum, compared to pooled control human serum induced the expression of Cbfa1 by RT-PCR in bovine VSMCs in a time-dependent, nonphosphorus-mediated mechanism.


CONCLUSIONS
These results support that Cbfa1 is a key regulatory factor in the vascular calcification observed in dialysis patients and is up-regulated in response to many uremic toxins.
Moe
Sharon M
SM
Department of Medicine, Indiana University School of Medicine and Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA. smoe@iupui.edu
Duan
Danxia
D
Doehle
Brian P
BP
O'Neill
Kalisha D
KD
Chen
Neal X
NX
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002114:Calcinosis / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit; D019074:Epigastric Arteries / Q000473:pathology* / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000473:pathology*; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014511:Uremia / Q000473:pathology*
D001798:Blood Proteins; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D014157:Transcription Factors; D053495:Osteopontin