Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. Selenomethionine (SeMet) is an organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response by both bolstering the endogenous thioredoxin and glutathione antioxidant defence systems and by directly scavenging damaging oxidant species. This study evaluated the effect of dietary SeMet supplementation within a high fat diet fed apolipoprotein E deficient (ApoE^−/-) mouse model of atherosclerosis. Dietary supplementation with SeMet (2 mg/kg) increased the tissue concentration of Se, and the expression and activity of glutathione peroxidase, compared to non-supplemented controls. Supplementation with SeMet significantly reduced atherosclerotic plaque formation in mouse aortae, resulted in a more stable lesion phenotype and improved vessel function. Concurrent with these results, SeMet supplementation decreased lesion accumulation of M1 inflammatory type macrophages, and decreased the extent of extracellular trap release from phorbol myristate acetate (PMA)-stimulated mouse bone marrow-derived cells. Importantly, these latter results were replicated within ex-vivo experiments on cultured neutrophils isolated from acute coronary syndrome patients, indicating the ability of SeMet to alter the acute inflammatory response within a clinically-relevant setting. Together, these data highlight the potential beneficial effect of SeMet supplementation as a therapeutic strategy for atherosclerosis.

动脉粥样硬化是脉管系统的慢性炎性疾病，其特征在于活化的嗜中性粒细胞和巨噬细胞在血管壁内损伤部位的浸润，这有助于病变的形成和斑块的进展。硒蛋氨酸（SeMet）是硒（Se）的有机形式，是必需的微量元素，可通过增强内源性硫氧还蛋白和谷胱甘肽抗氧化剂防御系统并直接清除有害的氧化剂来调节免疫应答。这项研究评估了补充高脂饮食的载脂蛋白E缺乏症（ApoE ^-/-）动脉粥样硬化的小鼠模型。与未补充营养的对照组相比，膳食补充SeMet（2 mg / kg）可以提高Se的组织浓度以及谷胱甘肽过氧化物酶的表达和活性。补充SeMet可显着减少小鼠主动脉粥样硬化斑块的形成，从而使病变表型更加稳定，血管功能得到改善。与这些结果同时，SeMet补充减少了M1炎性巨噬细胞的病灶积聚，并降低了佛波肉豆蔻酸酯醋酸盐（PMA）刺激的小鼠骨髓来源的细胞释放胞外陷阱的程度。重要的是，这些后一结果已在离体体内复制从急性冠状动脉综合征患者中分离出的培养性嗜中性粒细胞的实验表明，SeMet在临床相关环境中改变急性炎症反应的能力。总之，这些数据强调了SeMet补充作为动脉粥样硬化的治疗策略的潜在有益作用。