Liu Yu-Wei, Zuo Pei-Yuan, Zha Xiang-Nan, Chen Xing-Lin, Zhang Rong, He Xiao-Xiao, Liu Cheng-Yun
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China.
Lipids. 2015 Mar;50(3):241-51. doi: 10.1007/s11745-015-3991-2. Epub 2015 Feb 1.
Atherosclerosis is characterized by endothelial dysfunction, lipid deposition, fibro-proliferative reactions and inflammation. Octacosanol is a high-molecular-weight primary aliphatic alcohol. As the main component of a cholesterol-lowering drug, octacosanol could inhibit lipids accumulation and cholesterol metabolism. To explore the indication of octacosanol on endothelial protection, we evaluated its effects on the proliferation and migration of human umbilical vein endothelial cells (HUVEC). Cell viability assay using methyl thiazolyl tetrazolium and 5-ethynyl-2'-deoxyuridine revealed that 3.125 μg/ml octacosanol promoted the proliferation of HUVEC. A cell migration assay indicated that 0.781 and 3.125 μg/ml octacosanol increased the migration of HUVEC. Moreover, the phosphorylation levels of Akt and Erk1/2 were significantly elevated under exposure to octacosanol. Blocking the activation of Akt and Erk with their potent inhibitors LY294002 and PD98059, respectively, markedly attenuated the octacosanol-induced proliferation and migration of HUVEC. These findings demonstrated for the first time that octacosanol enhanced the proliferation and migration of HUVEC and mediated these effects through activation of the PI3K/Akt and MAPK/Erk1/2 signaling pathways.
动脉粥样硬化的特征是内皮功能障碍、脂质沉积、纤维增殖反应和炎症。二十八烷醇是一种高分子量的伯脂肪醇。作为一种降胆固醇药物的主要成分，二十八烷醇可以抑制脂质积累和胆固醇代谢。为了探究二十八烷醇在内皮保护方面的适应症，我们评估了其对人脐静脉内皮细胞（HUVEC）增殖和迁移的影响。使用甲基噻唑基四氮唑和5-乙炔基-2'-脱氧尿苷进行的细胞活力测定表明，3.125μg/ml的二十八烷醇促进了HUVEC的增殖。细胞迁移试验表明，0.781和3.125μg/ml的二十八烷醇增加了HUVEC的迁移。此外，在暴露于二十八烷醇的情况下，Akt和Erk1/2的磷酸化水平显著升高。分别用其强效抑制剂LY294002和PD98059阻断Akt和Erk的激活，显著减弱了二十八烷醇诱导的HUVEC增殖和迁移。这些发现首次证明，二十八烷醇增强了HUVEC的增殖和迁移，并通过激活PI3K/Akt和MAPK/Erk1/2信号通路介导了这些作用。
