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Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1

  • Authors:
    • Ping Wang
    • Zhengli Quan
    • Dingshi Luo
    • Wangshan Chen
    • Dan Peng
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China, Department of Neonatology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3622-3632
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    Published online on: March 15, 2019
       https://doi.org/10.3892/mmr.2019.10039
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Abstract

Vascular calcification (VC) is highly prevalent in chronic kidney disease (CKD), especially in patients with end stage renal disease and is strongly associated with cardiovascular morbidity and mortality. Clinical observations have demonstrated that hyperphosphatemia and hyperglycemia can accelerate VC. Spironolactone (SPL) has been proven to improve cardiovascular outcomes in clinical trials and its protective effect on VC has been reported recently; however, the underlying mechanisms are not completely understood and require further investigation. Furthermore, the current CKD rat models that are used to research VC do not match well with the clinical characteristics of CKD patients. Aortic rings were obtained from male Sprague‑Dawley rats, then cultured in different media with varying phosphorus and glucose concentrations to investigate the effects and the possible mechanisms, as well as the effective serum concentrations of SPL, on VC and type III sodium‑dependent phosphate cotransporter‑1 (Pit‑1) expression. SPL dose‑dependently alleviated VC by suppressing the phenotypic transition of vascular smooth muscle cell (VSMCs) through downregulation of Pit‑1 in a high phosphorus medium and even in a high phosphorus combined with high glucose medium. The combined effects of hyperglycemia and hyperphosphatemia on the calcification of aortic rings ex vivo were demonstrated. In conclusion to the best of our knowledge, this article is the first report on the effective serum concentrations of SPL capable of protecting VSMCs from calcification and provides the first experimental evidence for the combined effects of hyperglycemia and hyperphosphatemia on VC of aortic rings. Additionally, the Pit‑1 protein level may be a novel index for evaluating the magnitude of VC in CKD patients.
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Copy and paste a formatted citation
Spandidos Publications style
Wang P, Quan Z, Luo D, Chen W and Peng D: Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1. Mol Med Rep 19: 3622-3632, 2019.
APA
Wang, P., Quan, Z., Luo, D., Chen, W., & Peng, D. (2019). Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1. Molecular Medicine Reports, 19, 3622-3632. https://doi.org/10.3892/mmr.2019.10039
MLA
Wang, P., Quan, Z., Luo, D., Chen, W., Peng, D."Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1". Molecular Medicine Reports 19.5 (2019): 3622-3632.
Chicago
Wang, P., Quan, Z., Luo, D., Chen, W., Peng, D."Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1". Molecular Medicine Reports 19, no. 5 (2019): 3622-3632. https://doi.org/10.3892/mmr.2019.10039
Copy and paste a formatted citation
x
Spandidos Publications style
Wang P, Quan Z, Luo D, Chen W and Peng D: Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1. Mol Med Rep 19: 3622-3632, 2019.
APA
Wang, P., Quan, Z., Luo, D., Chen, W., & Peng, D. (2019). Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1. Molecular Medicine Reports, 19, 3622-3632. https://doi.org/10.3892/mmr.2019.10039
MLA
Wang, P., Quan, Z., Luo, D., Chen, W., Peng, D."Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1". Molecular Medicine Reports 19.5 (2019): 3622-3632.
Chicago
Wang, P., Quan, Z., Luo, D., Chen, W., Peng, D."Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1". Molecular Medicine Reports 19, no. 5 (2019): 3622-3632. https://doi.org/10.3892/mmr.2019.10039
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