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• W2106223721 abstract "Klotho-knockout mice (klotho(-/-)) have increased renal expression of sodium/phosphate cotransporters (NaPi2a), associated with severe hyperphosphatemia. Such serum biochemical changes in klotho(-/-) mice lead to extensive soft-tissue anomalies and vascular calcification. To determine the significance of increased renal expression of the NaPi2a protein and concomitant hyperphosphatemia and vascular calcification in klotho(-/-) mice, we generated klotho and NaPi2a double-knockout (klotho(-/-)/NaPi2a(-/-)) mice.Genetic inactivation of NaPi2a activity from klotho(-/-) mice reversed the severe hyperphosphatemia to mild hypophosphatemia or normophosphatemia. Importantly, despite significantly higher serum calcium and 1,25-dihydroxyvitamin D levels in klotho(-/-)/NaPi2a(-/-) mice, the vascular and soft-tissue calcifications were reduced. Extensive soft-tissue anomalies and cardiovascular calcification were consistently noted in klotho(-/-) mice by 6 weeks of age; however, these vascular and soft-tissue abnormalities were absent even in 12-week-old double-knockout mice. Klotho(-/-)/NaPi2a(-/-) mice also regained body weight and did not develop the generalized tissue atrophy often noted in klotho(-/-) single-knockout mice.Our in vivo genetic manipulation studies have provided compelling evidence for a pathological role of increased NaPi2a activities in regulating abnormal mineral ion metabolism and soft-tissue anomalies in klotho(-/-) mice. Notably, our results suggest that serum phosphate levels are the important in vivo determinant of calcification and that lowering serum phosphate levels can reduce or eliminate soft-tissue and vascular calcification, even in presence of extremely high serum calcium and 1,25-dihydroxyvitamin D levels. These in vivo observations have significant clinical importance and therapeutic implications for patients with chronic kidney disease with cardiovascular calcification." @default.
• W2106223721 created "2016-06-24" @default.
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• W2106223721 creator A5062845949 @default.
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• W2106223721 date "2009-12-01" @default.
• W2106223721 modified "2023-10-06" @default.
• W2106223721 title "In Vivo Genetic Evidence for Suppressing Vascular and Soft-Tissue Calcification Through the Reduction of Serum Phosphate Levels, Even in the Presence of High Serum Calcium and 1,25-Dihydroxyvitamin D Levels" @default.
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• W2106223721 doi "https://doi.org/10.1161/circgenetics.108.847814" @default.
• W2106223721 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2801877" @default.
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• W2106223721 hasPublicationYear "2009" @default.
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