Chen Zhen, Martin Marcy, Li Zhao, Shyy John Y-J
aDivision of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, California bBiochemistry and Molecular Biology Graduate Program, University of California, Riverside, Riverside, California, USA cCardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Curr Opin Lipidol. 2014 Oct;25(5):339-49. doi: 10.1097/MOL.0000000000000107.
Great effort has been devoted to elucidate the molecular mechanisms by which inflammasome in macrophages contributes to atherosclerosis. Inflammasome in vascular endothelial cells and its causal relationship with endothelial dysfunction in atherosclerosis are less understood. Here, we review the recent studies of inflammasome and its activation in endothelial cells, 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, a master regulator in cholesterol biosynthesis, can be activated in a noncanonical manner, which leads to the activation of the NOD-like receptor family pyrin domain-containing protein inflammasome in macrophages and endothelial cells. Results from in-vitro and in-vivo models suggest that sterol regulatory element-binding protein 2 is a key molecule in aggravating proinflammatory responses in endothelial cells and promoting atherosclerosis.
The SREBP-induced NOD-like receptor family pyrin domain-containing protein 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.
人们已付出巨大努力来阐明巨噬细胞中的炎性小体促成动脉粥样硬化的分子机制。血管内皮细胞中的炎性小体及其与动脉粥样硬化中内皮功能障碍的因果关系则鲜为人知。在此，我们综述了炎性小体及其在内皮细胞中激活的最新研究，并强调了动脉粥样硬化中的这种内皮炎症反应。
炎性小体是天然免疫中的关键效应物，它们在巨噬细胞和动脉壁中的激活促成动脉粥样硬化的发生。胆固醇生物合成的主要调节因子固醇调节元件结合蛋白2（SREBP-2）可通过非经典方式被激活，这会导致巨噬细胞和内皮细胞中含NOD样受体家族吡咯结构域蛋白炎性小体的激活。体外和体内模型的结果表明，SREBP-2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诱导的含NOD样受体家族吡咯结构域蛋白炎性小体及其对天然免疫的激发是动脉粥样硬化的重要促成因素。阐明其潜在机制将扩展我们对内皮功能障碍及其与血管炎症动态相互作用的理解。此外，靶向SREBP-炎性小体途径可能是减轻动脉粥样硬化的一种治疗策略。
