Angiotensin II promotes NO production, inhibits apoptosis and enhances adhesion potential of bone marrow-derived endothelial progenitor cells
Angiotensin II promotes NO production, inhibits apoptosis and enhances adhesion potential of bone marrow-derived endothelial progenitor cells
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DOI：
10.1038/cr.2008.69
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发表时间：
2008-06
期刊：
影响因子：
44.1
通讯作者：
Tao Yin;Xinliang Ma;Li Zhao;K. Cheng;Haichang Wang
中科院分区：
文献类型：
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作者：
Tao Yin;Xinliang Ma;Li Zhao;K. Cheng;Haichang Wang
内皮祖细胞（Endothelial progenitor cells, EPCs）参与了组织缺血和内皮损伤后新生血管和再内皮化的过程。EPCs的水平与心血管疾病的预后直接相关，并可能受到刺激或抑制因子的调节。鉴于血管紧张素II （AngII）与心血管系统之间的密切关系，我们研究了AngII对骨髓（BM）来源的EPCs活性的影响。采用密度梯度离心法从大鼠骨髓中分离细胞。AngII显著促进一氧化氮（NO）释放，抑制EPC凋亡，增强EPC粘附电位。缬沙坦或L-NAME预处理可减弱所有这些血管内皮细胞介导的影响。LY294002和wortmannin均能消除AngII的抗凋亡作用。Western blot分析显示，内皮NO合成酶（eNOS）蛋白和磷酸化Akt随着AngII处理在EPCs中升高。因此，AngII通过AngII 1型受体（AT1R）改善了EPCs的几种活性，这可能代表了AngII和AT1R与血管生成联系的可能机制。此外，血管内皮细胞通过eNOS合成一氧化氮调控细胞凋亡和粘附，pi3 -激酶/Akt通路在血管内皮细胞诱导的抗凋亡信号传导中发挥重要作用。
Endothelial progenitor cells (EPCs) participate in the processes of postnatal neovascularization and re-endothelialization in response to tissue ischemia and endothelial injury. The level of EPCs present has been found to be directly associated with the outcome of cardiovascular diseases, and could be regulated by stimulatory or inhibitory factors. Given the close relationship between angiotensin II (AngII) and the cardiovascular system, we investigated the effect of AngII on the activities of bone marrow (BM)-derived EPCs. Cells were isolated from BM of rats by density gradient centrifugation. Administration of AngII significantly promoted nitric oxide (NO) release, inhibited EPC apoptosis and enhanced EPC adhesion potential. All of these AngII-mediated effects on EPCs were attenuated by pretreatment with valsartan or L-NAME. Moreover, both LY294002 and wortmannin abolished the anti-apoptotic effect of AngII. Western blot analyses indicated that endothelial NO synthase (eNOS) protein and phosphorylated Akt increased with the treatment of AngII in EPCs. Thus, AngII improved several activities of EPCs through AngII type 1 receptor (AT1R), which may represent a possible mechanism linking AngII and AT1R with angiogenesis. Additionally, AngII-induced NO synthesis through eNOS in EPCs regulates apoptosis and adhesion, and the PI3-kinase/Akt pathway has an essential role in AngII-induced antiapoptosis signaling.