Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
The First Clinical Medical College, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Int J Nanomedicine. 2020 Jun 23;15:4501-4521. doi: 10.2147/IJN.S255392. eCollection 2020.
Elevation of blood homocysteine (Hcy) level (hyperhomocysteinemia) is a risk factor for cardiovascular disorders and is closely associated with endothelial dysfunction. The present study aims to investigate the protective effect and underlying mechanism of nanoscale selenium (Nano-Se) in Hcy-mediated vascular endothelial cell dysfunction in vitro and in vivo.
By incubating vascular endothelial cells with exogenous Hcy and generating hyperhomocysteinemic rat model, the effects of Nano-Se on hyperhomocysteinemia-mediated endothelial dysfunction and its essential mechanisms were investigated.
Nano-Se inhibited Hcy-induced mitochondrial oxidative damage and apoptosis by preventing the downregulation of glutathione peroxidase enzyme 1 and 4 (GPX1, GPX4) in the vascular endothelial cells, thus effectively prevented the vascular damage in vitro and in vivo in the hyperhomocysteinemic rats. Nano-Se possessed similar protective effects but lower toxicity against Hcy in vascular endothelial cells when compared with other forms of Se.
The application of Nano-Se could serve as a novel promising strategy against Hcy-mediated vascular dysfunction with reduced risk of Se toxicity.
血液同型半胱氨酸(Hcy)水平升高(高同型半胱氨酸血症)是心血管疾病的危险因素,与血管内皮功能障碍密切相关。本研究旨在探讨纳米硒(Nano-Se)在体外和体内 Hcy 介导的血管内皮细胞功能障碍中的保护作用及其潜在机制。
通过孵育血管内皮细胞与外源性 Hcy 并生成高同型半胱氨酸血症大鼠模型,研究了 Nano-Se 对高同型半胱氨酸血症介导的内皮功能障碍及其基本机制的影响。
Nano-Se 通过防止血管内皮细胞中谷胱甘肽过氧化物酶 1 和 4(GPX1、GPX4)的下调,抑制 Hcy 诱导的线粒体氧化损伤和细胞凋亡,从而有效预防了体外和体内高同型半胱氨酸血症大鼠的血管损伤。与其他形式的硒相比,Nano-Se 对血管内皮细胞中的 Hcy 具有相似的保护作用,但毒性较低。
应用 Nano-Se 可能成为一种新的有前途的策略,可降低硒毒性风险,对抗 Hcy 介导的血管功能障碍。