caa a22 4500 605521417 CHVBK 20210128100740.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00223-014-9929-5 doi (NATIONALLICENCE)springer-10.1007/s00223-014-9929-5 Phosphate Binders Prevent Phosphate-Induced Cellular Senescence of Vascular Smooth Muscle Cells and Vascular Calcification in a Modified, Adenine-Based Uremic Rat Model [Elektronische Daten] [S. Yamada, N. Tatsumoto, M. Tokumoto, H. Noguchi, H. Ooboshi, T. Kitazono, K. Tsuruya] 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. Springer Science+Business Media New York, 2014 Calcium carbonate nationallicence Cellular senescence nationallicence Chronic kidney disease nationallicence Phosphate nationallicence Phosphate binder nationallicence Vascular smooth muscle cell nationallicence Vascular calcification nationallicence Yamada S. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut Tatsumoto N. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut Tokumoto M. Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan aut Noguchi H. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut Ooboshi H. Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan aut Kitazono T. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut Tsuruya K. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut Calcified Tissue International Springer US; http://www.springer-ny.com 96/4(2015-04-01), 347-358 0171-967X 96:4<347 2015 96 223 https://doi.org/10.1007/s00223-014-9929-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-014-9929-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamada S. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 700 1- Tatsumoto N. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 700 1- Tokumoto M. Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan aut NATIONALLICENCE 700 1- Noguchi H. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 700 1- Ooboshi H. Department of Internal Medicine, Fukuoka Dental College, 814-0193, Fukuoka, Japan aut NATIONALLICENCE 700 1- Kitazono T. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 700 1- Tsuruya K. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 96/4(2015-04-01), 347-358 0171-967X 96:4<347 2015 96 223