Regulation of endothelial progenitor cell differentiation and function by dimethylarginine dimethylaminohydrolase 2 in an asymmetric dimethylarginine-independent manner.

Autor: Yuan Q; Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China., Bai YP, Shi RZ, Liu SY, Chen XM, Chen L, Li YJ, Hu CP
Jazyk: angličtina
Zdroj: Cell biology international [Cell Biol Int] 2014 Sep; Vol. 38 (9), pp. 1013-22. Date of Electronic Publication: 2014 May 16.
DOI: 10.1002/cbin.10288
Abstrakt: Endothelial progenitor cells (EPCs) are involved in the repair of vessels and angiogenesis and are useful in the treatment of ischemic diseases. The dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is regulated by silent information regulator 1 (SIRT1), leading to the senescence of endothelial cells (ECs). Here, we demonstrated that peripheral blood EPCs predominantly expressed DDAH2 that increased with EPC differentiation. EPC senescence and dysfunction were induced on interruption of DDAH2 expression, whereas the mRNA expression of vascular endothelial growth factor (VEGF) and kinase-domain insert containing receptor (KDR) were downregulated. Moreover, SIRT1 expression increased with EPC differentiation. Interruption of SIRT1 inhibited DDAH2, VEGF, and KDR expression, but had no effect on the level of ADMA. From our data, we concluded that DDAH2 is involved in the differentiation of EPCs and regulates the senescence and function of EPCs through the VEGF/KDR pathway by activation of SIRT1.
(© 2014 International Federation for Cell Biology.)
Databáze: MEDLINE
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