Regulation of endothelial progenitor cell differentiation and function by dimethylarginine dimethylaminohydrolase 2 in an asymmetric dimethylarginine-independent manner.
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.
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.
Qiong
Q
Yuan
Yong-Ping
YP
Bai
Rui-Zheng
RZ
Shi
Si-Yu
SY
Liu
Xu-Meng
XM
Chen
Lei
L
Chen
Yuan-Jian
YJ
Li
Chang-Ping
CP
Hu
D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C018524:N,N-dimethylarginine; D001120:Arginine; D040301:Vascular Endothelial Growth Factor Receptor-2; D000581:Amidohydrolases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C059999:dimethylargininase
SIRT1; dimethylarginine dimethylaminohydrolase; endothelial progenitor cells; senescence