Liu Shumin, Sun Zhengwu, Chu Peng, Li Hailong, Ahsan Anil, Zhou Ziru, Zhang Zonghui, Sun Bin, Wu Jingjun, Xi Yalin, Han Guozhu, Lin Yuan, Peng Jinyong, Tang Zeyao
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Pharmacy Department, Dalian Municipal Central Hospital, Dalian, China.
Apoptosis. 2017 May;22(5):672-680. doi: 10.1007/s10495-017-1360-8.
Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study. The study has demonstrated that EGCG suppressed Hcy-induced endothelial cell morphological changes and reactive oxygen species (ROS) generation. Moreover, EGCG dose-dependently prevented Hcy-induced HUVECs cytotoxicity and apoptotic biochemical changes such as reducing mitochondrial membrane potential (MMP), decreasing Bcl-2/Bax protein ratio and activating caspase-9 and 3. In addition, EGCG enhanced the protein ratio of p-Akt/Akt, endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) formation in injured cells. In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy).
同型半胱氨酸（Hcy）诱导的血管内皮损伤会导致动脉粥样硬化中内皮功能障碍的进展。表没食子儿茶素没食子酸酯（EGCG）是一种天然的膳食抗氧化剂，已被用于预防动脉粥样硬化。然而，EGCG潜在的保护机制尚未阐明。本研究探讨了EGCG保护细胞免受Hcy诱导的人脐静脉内皮细胞（HUVECs）凋亡的机制。本研究采用了甲基噻唑基四氮唑法（MTT）、透射电子显微镜、荧光染色、流式细胞术和蛋白质免疫印迹法。研究表明，EGCG可抑制Hcy诱导的内皮细胞形态变化和活性氧（ROS）生成。此外，EGCG剂量依赖性地预防了Hcy诱导的HUVECs细胞毒性和凋亡生化变化，如降低线粒体膜电位（MMP）、降低Bcl-2/Bax蛋白比值以及激活caspase-9和caspase-3。此外，EGCG提高了损伤细胞中p-Akt/Akt的蛋白比值、内皮型一氧化氮合酶（eNOS）的活性以及一氧化氮（NO）的生成。总之，本研究表明，EGCG通过调节线粒体凋亡和PI3K/Akt/eNOS信号通路来预防Hcy诱导的HUVECs凋亡。此外，研究结果表明，EGCG可能是一种针对高同型半胱氨酸血症（HHcy）相关动脉粥样硬化的潜在治疗策略。
