Abstract
The toxicity of doxorubicin to the cardiovascular system often limits its benefits and widespread use as chemotherapy. The mechanisms involved in doxorubicin-induced cardiovascular damage and possible protective interventions are not well-explored. Using human aortic endothelial cells, we show vitamin D3 strongly attenuates doxorubicin-induced senescence and cell cycle arrest. We further show the protective effects of vitamin D3 are mediated by the upregulation of IL-10 and FOXO3a expression through fine modulation of pAMPKα/SIRT1/FOXO3a complex activity. These results have great significance in finding a target for mitigating doxorubicin-induced cardiovascular toxicity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / genetics
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AMP-Activated Protein Kinases / metabolism
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Antibiotics, Antineoplastic / pharmacology
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Aorta / cytology
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Cells, Cultured
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Cellular Senescence / drug effects*
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Cellular Senescence / genetics
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Cholecalciferol / pharmacology*
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Doxorubicin / pharmacology*
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Forkhead Box Protein O3 / genetics
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Forkhead Box Protein O3 / metabolism
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Gene Expression / drug effects
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Humans
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Interleukin-10 / genetics
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Interleukin-10 / metabolism*
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Primary Cell Culture
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Proteins / genetics
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Proteins / metabolism*
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Signal Transduction / drug effects*
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Signal Transduction / genetics
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Sirtuin 1 / genetics
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Sirtuin 1 / metabolism
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Up-Regulation / drug effects
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Up-Regulation / genetics
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Vitamins / pharmacology
Substances
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Antibiotics, Antineoplastic
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Forkhead Box Protein O3
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Proteins
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Vitamins
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Interleukin-10
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Cholecalciferol
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Doxorubicin
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AMP-Activated Protein Kinases
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PRKAA1 protein, human
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Sirtuin 1