Sirolimus Induced Calcium Overload in Vascular Endothelial Cells via Ryanodine Receptor Pathway
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Pathological Department of Tianjin Institute of Medical Science, Tianjin 300020, China)

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R96

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    Abstract:

    Aim To investigate the effect and discuss its potential mechanism of sirolimus induced calcium overload and apoptosis in vascular endothelial cells. Methods Human umbilical vein endothelial cells(HUVEC) were exposed to sirolimus with or without intervention treatment with ryanodine. Effects on cell viability were assessed by the MTT assay. Effects on the production of nitric oxide(NO) were detected by nitric oxide assay kit. The intracellular calcium ion(Ca2+) concentration was assayed with Fluo-3 AM staining, changes of mitochondrial membrane potential were detected by JC-1 fluorescence labeling, HUVEC apoptosis rate was analyzed by Annexin V FITC/PI staining. ResultsCompared with the normal control group, the cell survival rate was decreased significantly in the treatments of sirolimus injury group(P<0.01). In sirolimus 500 nmol/L injury group, cell swelling, cytoplasm vacuoles, part of the nucleus pycnosis, nuclear fragmentation were observed by HE staining, levels of intracellular free Ca2+and cell apoptosis rate were increased(P<0.01), levels of NO and mitochondrial membrane potential were reduced(P<0.01). The intervention treatments, ryanodine, significantly reduced the sirolimus 500 nmol/L treatment-induced Ca2+(P<0.05) and cell apoptosis(43.3%±2.0% reduced to 30.7%±0.9%, P<0.01). Ryanodine also increased the sirolimus-treated cells’ viability(P<0.01), production of NO(28.33%±4.18 μmol/L increased to 47.03±3.87 μmol/L, P<0.01) and the level of mitochondrial membrane potential(0.24±0.03 increased to 0.45±0.04, P<0.01). Conclusion The possible mechanism of sirolimus induced calcium overload and apoptosis in HUVEC might be related to the increase of intracellular Ca2+ via ryanodine receptor pathway.

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YUAN Ling, NIE Wei, GAO Ping, LI Xin, LIU Wei-Wei, CUI Xiao-Xue. Sirolimus Induced Calcium Overload in Vascular Endothelial Cells via Ryanodine Receptor Pathway[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2016,24(2):129-134.

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History
  • Received:May 15,2015
  • Revised:July 27,2015
  • Online: June 30,2016
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