Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.
Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, Wuhan 430074, China.
Int J Mol Sci. 2021 Oct 27;22(21):11612. doi: 10.3390/ijms222111612.
Atherosclerosis and related cardiovascular diseases represent the greatest threats to human health, worldwide. Previous animal studies showed that selenium nanoparticles (SeNPs) and NaSeO might have anti-atherosclerotic activity, but the underlying mechanisms are poorly elucidated. This study compared the anti-atherosclerotic activity of SeNPs stabilized with chitosan (CS-SeNPs) and NaSeO and the related mechanism in a high-fat-diet-fed apolipoprotein E-deficient mouse model of atherosclerosis. The results showed that oral administration of both CS-SeNPs and NaSeO (40 μg Se/kg/day) for 10 weeks significantly reduced atherosclerotic lesions in mouse aortae. Mechanistically, CS-SeNPs and NaSeO not only alleviated vascular endothelial dysfunction, as evidenced by the increase of serum nitric oxide level and the decrease of aortic adhesion molecule expression, but also vascular inflammation, as evidenced by the decrease of macrophage recruitment as well as the expression of proinflammatory molecules. Importantly, these results were replicated within in-vivo experiments on the cultured human endothelial cell line EA.hy926. Overall, CS-SeNPs had a comparable effect with NaSeO but might have more potential in atherosclerosis prevention due to its lower toxicity. Together, these results provide more insights into the mechanisms of selenium against atherosclerosis and further highlight the potential of selenium supplementation as a therapeutic strategy for atherosclerosis.
动脉粥样硬化及相关心血管疾病是全世界范围内对人类健康的最大威胁。先前的动物研究表明,硒纳米粒子(SeNPs)和亚硒酸钠(NaSeO)可能具有抗动脉粥样硬化活性,但相关机制尚未阐明。本研究比较了壳聚糖稳定的硒纳米粒子(CS-SeNPs)和亚硒酸钠在动脉粥样硬化的载脂蛋白 E 缺陷型小鼠模型中的抗动脉粥样硬化活性及其相关机制。结果表明,连续 10 周口服 CS-SeNPs 和 NaSeO(40 μg Se/kg/天)均可显著减轻小鼠主动脉中的动脉粥样硬化病变。机制上,CS-SeNPs 和 NaSeO 不仅通过增加血清一氧化氮水平和降低主动脉黏附分子表达来减轻血管内皮功能障碍,还通过减少巨噬细胞募集和促炎分子表达来减轻血管炎症。重要的是,这些结果在体内实验中得到了培养的人脐静脉内皮细胞系 EA.hy926 的验证。总的来说,CS-SeNPs 与 NaSeO 具有相当的效果,但由于其毒性较低,在动脉粥样硬化预防方面可能具有更大的潜力。综上所述,这些结果为硒防治动脉粥样硬化的机制提供了更多的见解,并进一步强调了硒补充作为动脉粥样硬化治疗策略的潜力。