Guo Wei-Xin, Yang Qi-Dong, Liu Yun-Hai, Xie Xiao-Yun, Niu Rui-Chao
Department of Neurology, Xiangya Hospital of Central South University, Hunan Province, Changsha, China.
Arch Med Res. 2008 May;39(4):434-42. doi: 10.1016/j.arcmed.2008.02.001.
Endothelial progenitor cells (EPCs) are involved in adult neovasculogenesis and maintenance of vascular integrity. Scarce data have been provided for the individual effect of elevated free fatty acids (FFAs) on EPCs. This study was designed to investigate the association between Akt/eNOS signal pathway changes and the proliferation/function of EPCs in the presence of palmitic and linoleic acids.
After 14-day culture, EPCs were stimulated with different concentrations of palmitic and linoleic acids, with or without SNP, L-NAME, or LY294002. The proliferation and ability of adhesion, migration and tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed.
Incubation with palmitic and linoleic acids at concentrations of 0.2 muM or higher inhibited EPCs proliferation, significantly reduced migratory rate, reduced adhesion to fibronectin and impaired ability of EPCs to form tube structure in a dose-dependent manner. A simultaneous dose-dependent NO generation and Akt phosphorylation decrease as well as eNOS expression reduction at protein levels were also observed. However, all of the detrimental effects were attenuated by pretreating EPCs with SNP, NO donor. AKT and eNOS inhibitor, LY294002 and L-NAME, respectively, augmented palmitic and linoleic acids inhibitory effects on EPCs.
These findings suggest that palmitic and linoleic acids downregulated AKT/eNOS signal pathway, which contributed to overall poor function and decrease proliferation of EPCs. These changes induced by palmitic and linoleic acids in signaling offer a novel explanation for the overall poor function of EPCs in diabetes mellitus.
内皮祖细胞（EPCs）参与成人新血管生成和血管完整性的维持。关于游离脂肪酸（FFAs）升高对EPCs的个体影响，目前提供的数据较少。本研究旨在探讨在棕榈酸和亚油酸存在的情况下，Akt/eNOS信号通路变化与EPCs增殖/功能之间的关联。
培养14天后，用不同浓度的棕榈酸和亚油酸刺激EPCs，同时或不同时添加SNP、L-NAME或LY294002。观察EPCs的增殖、黏附、迁移和管腔形成能力，并检测磷酸化Akt蛋白表达水平和eNOS蛋白表达水平。
用0.2μM或更高浓度的棕榈酸和亚油酸孵育会抑制EPCs增殖，显著降低迁移率，减少对纤连蛋白的黏附，并以剂量依赖的方式损害EPCs形成管腔的能力。同时还观察到蛋白水平上NO生成、Akt磷酸化以及eNOS表达呈剂量依赖性降低。然而，用NO供体SNP预处理EPCs可减轻所有这些有害影响。AKT和eNOS抑制剂LY294002和L-NAME分别增强了棕榈酸和亚油酸对EPCs的抑制作用。
这些发现表明，棕榈酸和亚油酸下调了AKT/eNOS信号通路，这导致了EPCs整体功能不良和增殖减少。棕榈酸和亚油酸在信号传导中引起的这些变化为糖尿病中EPCs整体功能不良提供了一种新的解释。
