Endothelial dysfunction: the role of sterol regulatory element-binding protein-induced NOD-like receptor family pyrin domain-containing protein 3 inflammasome in atherosclerosis.
Endothelial dysfunction: the role of sterol regulatory element-binding protein-induced NOD-like receptor family pyrin domain-containing protein 3 inflammasome in atherosclerosis.
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DOI：
10.1097/mol.0000000000000107
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发表时间：
2014-10
影响因子：
4.4
通讯作者：
Shyy JY
中科院分区：
文献类型：
--
作者：
Chen Z;Martin M;Li Z;Shyy JY
巨噬细胞内炎性体参与动脉粥样硬化的分子机制已经得到了广泛的研究。血管内皮细胞（ECs）中的炎性体及其与动脉粥样硬化中内皮功能障碍的因果关系尚不清楚。在这里，我们回顾了炎症小体及其在内皮细胞中的激活的最新研究，并强调了动脉粥样硬化中的内皮炎症反应。炎性小体是先天免疫的关键效应器，它们在巨噬细胞和动脉壁中的激活有助于动脉粥样硬化的发生。甾醇调节元件结合蛋白2 （SREBP2）是胆固醇生物合成的主要调控因子，可以非规范方式激活，导致巨噬细胞和内皮细胞中炎症小体nod样受体家族pyrin结构域含蛋白（NLRP）的激活。体外和体内模型的结果表明，SREBP2是加重内皮细胞促炎反应和促进动脉粥样硬化的关键分子。srebp诱导的NLRP炎性体及其诱导的先天免疫是动脉粥样硬化的重要因素。阐明潜在的机制将扩大我们对内皮功能障碍及其与血管炎症的动态相互作用的理解。此外，靶向srebp -炎性体途径可能是一种减轻动脉粥样硬化的治疗策略。
Great effort has been devoted to elucidate the molecular mechanisms by which inflammasome in macrophages contributes to atherosclerosis. Inflammasome in vascular endothelial cells (ECs) and its causal relationship with endothelial dysfunction in atherosclerosis are less understood. Here we review recent studies of inflammasome and its activation in ECs, and highlight such endothelial inflammatory response in atherosclerosis. Inflammasomes are critical effectors in innate immunity, and their activation in macrophages and the arterial wall contributes to atherogenesis. Sterol regulatory element-binding protein 2 (SREBP2), a master regulator in cholesterol biosynthesis, can be activated in a non-canonical manner, which leads to activation of the inflammasome NOD-like receptor family pyrin domain-containing protein (NLRP) in macrophages and ECs. Results from in vitro and in vivo models suggest that SREBP2 is a key molecule in aggravating pro-inflammatory responses in ECs, and promoting atherosclerosis. The SREBP-induced NLRP inflammasome and its instigation of innate immunity is an important contributor to atherosclerosis. Elucidating the underlying mechanisms will expand our understanding of endothelial dysfunction and its dynamic interaction with vascular inflammation. Furthermore, targeting SREBP-inflammasome pathways can be a therapeutic strategy for attenuating atherosclerosis.