Combined effects of hyperphosphatemia and hyperglycemia on the calcification of cultured human aortic smooth muscle cells

Wang, Ping; Zhou, Ping; Chen, Wangshan; Peng, Dan

doi:10.3892/etm.2018.7024

Cited by 18 publications

(36 citation statements)

References 27 publications

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“…From another perspective, due to the complex mechanisms of VC, the authors insist on their premise that the experimental model should be as simple as possible to avoid the potential impact from unassociated components. Previously, human aortic smooth muscle cells were cultured in hyperglycemic and hyperphosphatemic media, and the combined effects of hyperphosphatemia and hyperglycemia were also observed on human aortic smooth muscle cell calcification (34). Regarding the above-mentioned results, it was concluded that there were combined effects of hyperglycemia and hyperphosphatemia on VSMC calcification, and it is considered to be a key explanation for why ESRD patients with diabetes mellitus exhibted shorter survival times/higher mortality rate (35–37).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…It was reported that high glucose could induce VSMC calcification ( Wang et al, 2019 ), so 25 mM glucose was used in this study. Cell calcification was examined by alizarin red staining, and the results showed that MOVAS cells exposed to 25 mM glucose showed significant calcification, as demonstrated by the increased numbers of deep red calcium nodules ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

Selenium-Containing Protein From Selenium-Enriched Spirulina platensis Attenuates High Glucose-Induced Calcification of MOVAS Cells by Inhibiting ROS-Mediated DNA Damage and Regulating MAPK and PI3K/AKT Pathways

Liu

Zhang

et al. 2020

Front. Physiol.

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Hyperglycemia is the main feature of diabetes and may increase the risk of vascular calcification (VC), which is an independent predictor for cardiovascular and cerebrovascular diseases (CCD). Selenium (Se) may decrease the risk of CCD, and previous studies confirmed that Se-containing protein from Se-enriched Spirulina platensis (Se-SP) exhibited novel antioxidant potential. However, the effect of Se-SP against VC has been not investigated. Herein, the protective effect and underlying mechanism of Se-SP against high glucose-induced calcification in mouse aortic vascular smooth muscle cells (MOVAS) were explored. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) results showed time-dependent uptake of Se-SP in MOVAS cells, which significantly inhibited high glucose-induced abnormal proliferation. Se-SP co-treatment also effectively attenuated high glucose-induced calcification of MOVAS cells, followed by decreased activity and expression of alkaline phosphatase (ALP). Further investigation revealed that Se-SP markedly prevented reactive oxygen species (ROS)-mediated DNA damage in glucose-treated MOVAS cells. ROS inhibition by glutathione (GSH) effectively inhibited high glucose-induced calcification, indicating that Se-SP could act as ROS inhibitor to inhibit high glucose-induced DNA damage and calcification. Moreover, Se-SP dramatically attenuated high glucose-induced dysfunction of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathways. Se-SP after Se addition achieved enhanced potential in inhibiting high glucose-induced calcification, which validated that Se-SP as a new Se species could be a highly effective treatment for human CCD.

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“…In accordance with previous reports [ 16 , 17 , 39 ], the present observations show that high glucose directly promotes the osteogenic transdifferentiation of VSMCs, although relatively high glucose concentrations were required. In in vitro models of high glucose-induced VSMC calcification, the glucose levels required to induce a response in VSMCs presumably vary with the different origins of the cells and/or the cell culture medium used in experiments [ 16 , 17 , 39 , 40 ]. The effects of high glucose conditions were not mimicked by mannitol, which has been used as an osmotic control for high glucose-induced VSMC calcification processes [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Role of SGK1 in the Osteogenic Transdifferentiation and Calcification of Vascular Smooth Muscle Cells Promoted by Hyperglycemic Conditions

Poetsch

Henze

Estepa

et al. 2020

IJMS

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In diabetes mellitus, hyperglycemia promotes the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) to enhance medial vascular calcification, a common complication strongly associated with cardiovascular disease and mortality. The mechanisms involved are, however, still poorly understood. Therefore, the present study explored the potential role of serum- and glucocorticoid-inducible kinase 1 (SGK1) during vascular calcification promoted by hyperglycemic conditions. Exposure to high-glucose conditions up-regulated the SGK1 expression in primary human aortic VSMCs. High glucose increased osteogenic marker expression and activity and, thus, promoted the osteogenic transdifferentiation of VSMCs, effects significantly suppressed by additional treatment with the SGK1 inhibitor EMD638683. Moreover, high glucose augmented the mineralization of VSMCs in the presence of calcification medium, effects again significantly reduced by SGK1 inhibition. Similarly, SGK1 knockdown blunted the high glucose-induced osteogenic transdifferentiation of VSMCs. The osteoinductive signaling promoted by high glucose required SGK1-dependent NF-κB activation. In addition, advanced glycation end products (AGEs) increased the SGK1 expression in VSMCs, and SGK1 inhibition was able to interfere with AGEs-induced osteogenic signaling. In conclusion, SGK1 is up-regulated and mediates, at least partly, the osteogenic transdifferentiation and calcification of VSMCs during hyperglycemic conditions. Thus, SGK1 inhibition may reduce the development of vascular calcification promoted by hyperglycemia in diabetes.

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Combined effects of hyperphosphatemia and hyperglycemia on the calcification of cultured human aortic smooth muscle cells

Cited by 18 publications

References 27 publications

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

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

Selenium-Containing Protein From Selenium-Enriched Spirulina platensis Attenuates High Glucose-Induced Calcification of MOVAS Cells by Inhibiting ROS-Mediated DNA Damage and Regulating MAPK and PI3K/AKT Pathways

Role of SGK1 in the Osteogenic Transdifferentiation and Calcification of Vascular Smooth Muscle Cells Promoted by Hyperglycemic Conditions

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