Involvement of dimethylarginine dimethylaminohydrolase-2 in visfatin-enhanced angiogenic function of endothelial cells.
BACKGROUND
Visfatin, a new adipocytokine, was reported to promote angiogenesis. Dimethylarginine dimethylaminohydrolase (DDAH), which could regulate vascular endothelial growth factor (VEGF) expression in endothelial cells, is thought as a novel modulator of angiogenesis. The aim of the study was to investigate the role of DDAH2 in visfatin-induced angiogenesis in human umbilical vein endothelial cells (HUVECs).


RESULTS
Visfatin could concentration- and time-dependently enhance cell migration and tube formation reflecting angiogenic capability of HUVECs. Moreover, visfatin upregulated both mRNA and protein expressions of DDAH2 and VEGF. Angiogenic effects of visfatin were attenuated by DDAH2 small interfering RNA. Visfatin-induced protein kinase B (Akt) phosphorylation and phosphoinositide 3 kinase (PI3K) inhibitors could suppress visfatin-induced upregulation of DDAH2 and VEGF expressions.


CONCLUSIONS
Taken together, our results demonstrate that PI3K/Akt-mediated upregulation of DDAH2 expression plays a critical role in visfatin-promoted angiogenesis via regulating VEGF-dependent pathway.
Xiao
Jian
J
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
Xiao
Zheng-Jun
ZJ
Liu
Zhen-Guo
ZG
Gong
Huan-Yu
HY
Yuan
Qiong
Q
Wang
Shan
S
Li
Yuan-Jian
YJ
Jiang
De-Jian
DJ
D000581:Amidohydrolases / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D054409:Nicotinamide Phosphoribosyltransferase / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D042461:Vascular Endothelial Growth Factor A; D054409:Nicotinamide Phosphoribosyltransferase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000581:Amidohydrolases; C059999:dimethylargininase