|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (2010) 34, S42 (Printed in Great Britain)
Regulatory effect of dimethylarginine dimethylaminohydrolase on endothelial progenitor cells differentiation and function
Qiong Yuan1, Chang‑Ping Hu12, Si‑Yu Liu1, Xu‑Meng Chen1, Jun Peng12 and Yuan‑Jian Li12
1Department of Pharmacology, Central South University, Changsha 410078, China, and 2Hunan Provincial Key Laboratory of Cardiovascular Research, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China
Endothelial progenitor cells (EPCs), which can differentiate into mature endothelial cells, promote neovascularization, participate in the preparation of vessels and angiogenesis, and are used for the treatment of ischemic diseases. Vascular endothelial growth factor (VEGF) is a potent factor regulating EPCs functions, including reendothelization and angiogenesis. The effects of VEGF have been shown to be mediated by type 2 VEGF receptor (KDR). It is know that dimethylarginine dimethylaminohydrolase (DDAH) metabolizes asymmetric dimethylarginine (ADMA), which is endogenous inhibitor of nitric oxide synthase (NOS) leading to inhibition of nitric oxide (NO) production. It has been demonstrated that the DDAH/ADMA pathway is involved in senescence of endothelial cell and angiogenesis. SIRT1, human silent information regulator 2 (Sir2), is a potent NAD+-dependent protein deacetylase and plays an important role in the maintenance of gene silencing. SIRT1 inhibits senescence of endothelial cells through the DDAH2/ADMA pathway. It has also been shown that SIRT1 is involved in the senescence of EPCs induced by high glucose. Based on the regulatory effect of DDAH/ADMA and SIRT1 on angiogenesis and cell senescence, and SIRT1-mediated the effect of DDAH/ADMA, therefore, in the present study we tested the effect of DDAH/ADMA and SIRT1 on senescence and function of EPCs. In this study, we demonstrated that peripheral blood-derived EPCs predominantly expressed DDAH2 which was increased with EPCs differentiation. Interrupting DDAH2 expression induced EPCs senescence and dysfunction including impairment of angiogenesis and adhesion, and the mRNA expression of VEGF and KDR was also down-regulated. The expression of SIRT1 was increased with EPCs differentiation. Interrupting SIRT1 inhibited the expressions of DDAH2, VEGF and KDR, but had no effect on the level of ADMA. In conclusion, DDAH2 participated in the differentiation of EPCs and regulated the senescence and function of EPCs through the VEGF/KDR pathway by the activation of SIRT1.
Published online 1 August 2010, doi:10.1042/CBI034S042b
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