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Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model.
MedLine Citation:
PMID:  22513315     Owner:  NLM     Status:  Publisher    
OBJECTIVES: Cardiovascular allografts in the young have limited durability because of early graft calcification. The objective of this study was to examine the hypothesis that growth-associated hyperphosphatemia in youth accelerates aortic allograft calcification by osteogenic transformation of graft medial smooth muscle cells (SMCs). METHODS: The descending aortas of donor rats were subcutaneously transplanted into recipients. Syngeneic (Lewis-to-Lewis) transplantations between 3-week-old "young" (Y) rats and between 10-week-old "adult" (A) rats were combined with standard (ST, 0.9% phosphate) and low-phosphate (LP, 0.2%) diets, resulting in Y-ST, Y-LP, and A-ST groups. Allotransplantations (Brown-Norway-to-Lewis) involving these ages and diets were also made. The grafts and sera were retrieved from recipients after 14 days. Cultured rat aortic SMCs were used to analyze the effects of tumor necrosis factor-alpha (TNF-α) and phosphate on SMC calcification. RESULTS: In vivo, serum phosphate levels were higher in Y-ST (11.5 mg/dL) than those in Y-LP (8.9 mg/dL) and A-ST (8.5 mg/dL). Graft medial calcification appeared severe only in Y-ST. Allotransplants did not affect these outcomes. Graft medial cells showed phenotypic changes (contractile to synthetic) and osteogenic transformation (α-smooth muscle actin to Runx2 and osteocalcin), together with up-regulated proinflammatory TNF-α and sodium-phosphate cotransporter, Pit-1, despite ages and diets. In vitro, TNF-α induced phenotypic changes and osteogenic transformation of SMCs with Pit-1 up-regulation, but SMC calcification occurred only with high phosphate (4.5 mmol/L). CONCLUSIONS: Growth-associated hyperphosphatemia with inflammatory responses may be essential for accelerating allograft calcification in youth and could be a therapeutic target.
Haruo Yamauchi; Noboru Motomura; Ung-Il Chung; Masataka Sata; Daiya Takai; Aya Saito; Minoru Ono; Shinichi Takamoto
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-17
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  -     ISSN:  1097-685X     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Department of Cardiothoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
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