Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway.
Endothelial progenitor cells (EPCs) play an important role in aging-associated senescence, thereby potentially contributing to vascular pathologies. Visfatin, identified as a new adipocytokine, is closely associated with the senescence of human cells. However, the effects of visfatin on the oxidized low-density lipoprotein (ox-LDL)-induced senescence of EPCs has not yet been explored, to the best of our knowledge. For this purpose, in the present study, we examined the effects of visfatin in ox-LDL-stimulated EPCs as well as the underlying mechanism responsible for these effects. We found that visfatin attenuated the ox-LDL-induced senescence of EPCs by repressing β-galactosidase expression and recovering telomerase activity. Western blot analysis confirmed that visfatin induced a dose-dependent increase in sirtuin 1 (SIRT1) expression in EPCs and ox-LDL exposure decreased SIRT1 expression. Silencing SIRT1 abolished the inhibition of EPC senescence and the suppression of p53 expression induced by visfatin. Moreover, visfatin attenuated the inhibition of phosphorylation of Akt, phosphoinositide-3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) induced by ox-LDL. Taken together, these findings suggest that the treatment of EPCs with visfatin markedly attenuates the ox-LDL-induced senescence of EPCs by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Guang-Feng
GF
Ming
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Yong-Jun
YJ
Tang
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Kai
K
Hu
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Yao
Y
Chen
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Wei-Hua
WH
Huang
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Jian
J
Xiao
D016922:Cellular Senescence / Q000187:drug effects*; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D008077:Lipoproteins, LDL; D016159:Tumor Suppressor Protein p53; C099252:oxidized low density lipoprotein; D054409:Nicotinamide Phosphoribosyltransferase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D056564:Sirtuin 1