Sun Ning, Wang Hui, Wang Lin
Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute Tianjin 300052, China.
Department of Geriatrics, The second hospital of Tianjin Medical University Tianjin 300211, China.
Int J Clin Exp Pathol. 2015 Jan 1;8(1):482-9. eCollection 2015.
Improving the dysfunction of endothelial progenitor cell (EPCs) in patients with diabetes mellitus is important for preventing vascular complication. Vaspin, an adipocytokine, has the anti-atherogenic properties rely on its positive effect on nitric oxide (NO) bioavailability. We hypothesis that vaspin may ameliorate high glucose induced dysfunction of EPCs. In rat bone marrow derived EPCs, glucose treatment results in a decrease in the proliferation and migration capacity in a dose dependent manner. These detrimental effects can be alleviated by vaspin. Furthermore, vaspin increased the production of NO and the effect of vaspin on EPCs can be diminished partly by the eNOS inhibitor (L-NAME). We assessed total eNOS protein expression and Ser(1177)-phospho-eNOS expression and found that vaspin not only induced eNOS protein expression but also up regulate the eNOS activation. Subsequently, we investigated protein kinase B (Akt) activation in the presence and absence of phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor (LY-2940002). Vaspin increased total Akt and Ser(473)-phospho-Akt expression and these effects can be blocked by LY-2940002. The results of our study indicate a novel effect of vaspin to regulate eNOS expression and function in EPCs via a PI3K/Akt/eNOS pathway; vaspin may have a protective effect in patients with diabetes to prevent the occurrence of vascular complication.
改善糖尿病患者内皮祖细胞（EPCs）功能障碍对于预防血管并发症至关重要。内脏脂肪素（vaspin）是一种脂肪细胞因子，具有抗动脉粥样硬化特性，其依赖于对一氧化氮（NO）生物利用度的积极作用。我们推测vaspin可能改善高糖诱导的EPCs功能障碍。在大鼠骨髓来源的EPCs中，葡萄糖处理导致增殖和迁移能力呈剂量依赖性下降。这些有害作用可被vaspin减轻。此外，vaspin增加了NO的产生，并且eNOS抑制剂（L-NAME）可部分减弱vaspin对EPCs的作用。我们评估了总eNOS蛋白表达和Ser(1177)-磷酸化eNOS表达，发现vaspin不仅诱导eNOS蛋白表达，还上调eNOS活性。随后，我们在有和没有磷脂酰肌醇3-激酶（PI 3-激酶）抑制剂（LY-2940002）的情况下研究了蛋白激酶B（Akt）的激活情况。Vaspin增加了总Akt和Ser(473)-磷酸化Akt的表达，并且这些作用可被LY-2940002阻断。我们的研究结果表明vaspin通过PI3K/Akt/eNOS途径对调节EPCs中eNOS表达和功能具有新的作用；vaspin可能对糖尿病患者预防血管并发症的发生具有保护作用。
