Yuan Qiong, Bai Yong-Ping, Shi Rui-Zheng, Liu Si-Yu, Chen Xu-Meng, Chen Lei, Li Yuan-Jian, Hu Chang-Ping
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.
Cell Biol Int. 2014 Sep;38(9):1013-22. doi: 10.1002/cbin.10288. Epub 2014 May 16.
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.
内皮祖细胞（EPCs）参与血管修复和血管生成，在缺血性疾病治疗中具有重要作用。二甲基精氨酸二甲胺水解酶（DDAH）/不对称二甲基精氨酸（ADMA）通路受沉默信息调节因子1（SIRT1）调控，可导致内皮细胞（ECs）衰老。在此，我们发现外周血EPCs主要表达DDAH2，且其表达随EPC分化而增加。DDAH2表达中断可诱导EPC衰老和功能障碍，同时血管内皮生长因子（VEGF）和含激酶结构域插入受体（KDR）的mRNA表达下调。此外，SIRT1表达也随EPC分化而增加。SIRT1表达中断会抑制DDAH2、VEGF和KDR表达，但对ADMA水平无影响。根据我们的数据，我们得出结论：DDAH2参与EPC分化，并通过激活SIRT1经VEGF/KDR通路调节EPC的衰老和功能。
