Phosphate Binders Prevent Phosphate-Induced Cellular Senescence of Vascular Smooth Muscle Cells and Vascular Calcification in a Modified, Adenine-Based Uremic Rat Model

Verfasser / Beitragende:
[S. Yamada, N. Tatsumoto, M. Tokumoto, H. Noguchi, H. Ooboshi, T. Kitazono, K. Tsuruya]
Ort, Verlag, Jahr:
2015
Enthalten in:
Calcified Tissue International, 96/4(2015-04-01), 347-358
Format:
Artikel (online)
ID: 605521417
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024 7 0 |a 10.1007/s00223-014-9929-5  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00223-014-9929-5 
245 0 0 |a Phosphate Binders Prevent Phosphate-Induced Cellular Senescence of Vascular Smooth Muscle Cells and Vascular Calcification in a Modified, Adenine-Based Uremic Rat Model  |h [Elektronische Daten]  |c [S. Yamada, N. Tatsumoto, M. Tokumoto, H. Noguchi, H. Ooboshi, T. Kitazono, K. Tsuruya] 
520 3 |a Clinical and experimental studies have reported that phosphate overload plays a central role in the pathogenesis of vascular calcification in chronic kidney disease. However, it remains undetermined whether phosphate induces cellular senescence during vascular calcification. We established a modified uremic rat model induced by a diet containing 0.3% adenine that showed more slowly progressive kidney failure, more robust vascular calcification, and longer survival than the conventional model (0.75% adenine). To determine the effect of phosphate on senescence of vascular smooth muscle cells (VSMCs) and the protective effect of phosphate binders, rats were divided into four groups: (1) normal control rats; (2) rats fed with the modified adenine-based diet (CKD); (3) CKD rats treated with 6% lanthanum carbonate (CKD-LaC); and (4) CKD rats treated with 6% calcium carbonate (CKD-CaC). After 8weeks, CKD rats showed circumferential arterial medial calcification, which was inhibited in CKD-LaC and CKD-CaC rats. CKD rats showed increased protein expression of senescence-associated β-galactosidase, bone-related proteins, p16 and p21, and increased oxidative stress levels in the calcified area, which were inhibited by both phosphate binders. However, serum levels of oxidative stress and inflammatory markers, serum fibroblast growth factor 23, and aortic calcium content in CKD-CaC rats were higher than those in CKD-LaC rats. In conclusion, phosphate induces cellular senescence of VSMCs in the modified uremic rat model, and phosphate binders can prevent both cellular senescence and calcification of VSMCs via phosphate unloading. Our modified adenine-based uremic rat model is useful for evaluating uremia-related complications, including vascular calcification. 
540 |a Springer Science+Business Media New York, 2014 
690 7 |a Calcium carbonate  |2 nationallicence 
690 7 |a Cellular senescence  |2 nationallicence 
690 7 |a Chronic kidney disease  |2 nationallicence 
690 7 |a Phosphate  |2 nationallicence 
690 7 |a Phosphate binder  |2 nationallicence 
690 7 |a Vascular smooth muscle cell  |2 nationallicence 
690 7 |a Vascular calcification  |2 nationallicence 
700 1 |a Yamada  |D S.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
700 1 |a Tatsumoto  |D N.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
700 1 |a Tokumoto  |D M.  |u Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan  |4 aut 
700 1 |a Noguchi  |D H.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
700 1 |a Ooboshi  |D H.  |u Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan  |4 aut 
700 1 |a Kitazono  |D T.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
700 1 |a Tsuruya  |D K.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
773 0 |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 96/4(2015-04-01), 347-358  |x 0171-967X  |q 96:4<347  |1 2015  |2 96  |o 223 
856 4 0 |u https://doi.org/10.1007/s00223-014-9929-5  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00223-014-9929-5  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yamada  |D S.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tatsumoto  |D N.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tokumoto  |D M.  |u Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Noguchi  |D H.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ooboshi  |D H.  |u Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kitazono  |D T.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tsuruya  |D K.  |u Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 96/4(2015-04-01), 347-358  |x 0171-967X  |q 96:4<347  |1 2015  |2 96  |o 223