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

• Published in: Nephrology, dialysis, transplantation Vol. 21; no. 4; pp. 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: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2006; Oxford Publishing Limited (England)
• 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; Endocrinopathy; Kidney disease; Urinary system disease; Rat; Hemodialysis; Rodentia; core-binding factor alpha-1 (Cbfal); vascular calcification; sodium-dependent phosphate cotransporter (Pit-1); Extrarenal dialysis; Vertebrata; Mammalia; Sodium phosphate; Parathyroid diseases; Animal; hyperphosphataemia; Renal failure; secondary hyperparathyroidism (SHPT); Calcification; Hyperparathyroidism
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfk008

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.