Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism

Background. Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence...

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Published in:Nephrology, dialysis, transplantation dialysis, transplantation, 2006-04, Vol.21 (4), p.911-916
Main Authors: Mizobuchi, Masahide, Ogata, Hiroaki, Hatamura, Ikuji, Koiwa, Fumihiko, Saji, Fumie, Shiizaki, Kazuhiro, Negi, Shigeo, Kinugasa, Eriko, Ooshima, Akira, Koshikawa, Shozo, Akizawa, Tadao
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Aorta, Abdominal
Aortic Diseases - metabolism
Biological and medical sciences
Calcinosis - metabolism
Core Binding Factor Alpha 1 Subunit - genetics
Core Binding Factor Alpha 1 Subunit - metabolism
core-binding factor alpha-1 (Cbfa1)
Emergency and intensive care: renal failure. Dialysis management
Endocrinopathies
Gene Expression Regulation
Hyperparathyroidism, Secondary - etiology
Hyperparathyroidism, Secondary - metabolism
hyperphosphataemia
Intensive care medicine
Male
Medical sciences
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases)
Phosphorus Metabolism Disorders - etiology
Phosphorus Metabolism Disorders - metabolism
Rats
Rats, Sprague-Dawley
Renal failure
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
secondary hyperparathyroidism (SHPT)
sodium-dependent phosphate cotransporter (Pit-1)
Sodium-Phosphate Cotransporter Proteins, Type III - genetics
Sodium-Phosphate Cotransporter Proteins, Type III - metabolism
Up-Regulation
vascular calcification
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Summary:Background. Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence of vascular calcification in ESKD, the pathogenesis of the disorder is still obscure. The present study examined the expressions of bone-associated factors in calcified arteries in subtotally nephrectomized rats with severe secondary hyperparathyroidism (SHPT). Methods. Seven-week-old male Sprague–Dawley rats were divided into five groups as follows: sham-operated rats that received a normal diet [0.8% of phosphorus (P), 1.1% of calcium (Ca)] (Sham), sham-operated rats that received a high-phosphorus and low-calcium (HPLCa) diet (1.2% P, 0.4% Ca) (Sham+HPLCa), 5/6 nephrectomized rats that received a normal diet as the uraemic control group (Nx), and 5/6 nephrectomized rats that received a HPLCa diet to induce the development of SHPT (Nx+HPLCa), and 5/6 nephrectomized and parathyroidectomized rats that received a HPLCa diet (Nx+PTx+HPLCa). The feeding period of each group was 10 weeks. The rats were then sacrificed and their serum was examined. The upper part of the abdominal aorta was used to investigate the expression of mRNAs of core-binding factor alpha-1 (Cbfa1) and sodium-dependent phosphate cotransporter (Pit-1) by real-time reverse transcriptase polymerase chain reaction (real-time PCR) analysis. The lower part was examined for calcification by von Kossa staining. Results. Serum P level and Ca × P products increased significantly in the Nx+HPLCa group compared with those of any other groups. Severe hyperparathyroidism was also observed in the Nx+HPLCa group. Vascular calcification (medial layer) was observed in the Nx+HPLCa group only. There was a significant increase in Cbfa1 and Pit-1 mRNA expression levels in the aorta of the Nx+HPLCa group compared with that of any other groups. Conclusions. These results suggest that medial layer vascular calcification in uraemic rats with severe hyperphosphataemia and SHPT may be caused in part by Cbfa1 and Pit-1.
ISSN:0931-0509
1460-2385
DOI:10.1093/ndt/gfk008