Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Curr Opin Lipidol. 2018 Oct;29(5):375-380. doi: 10.1097/MOL.0000000000000540.
Atherosclerosis is a chronic inflammatory disease in which subendothelial infiltration of lipoproteins leads to inflamed lesions in arteries. Despite improvements in secondary prevention, most cardiovascular events cannot be avoided with current therapies. This review focuses on novel mechanistic insights on lipid-driven immune activation, which could pave the way for new anti-inflammatory treatments for atherosclerosis.
Immunometabolic interactions can shape the immune response. Within atherosclerotic plaques, macrophages and T cells are the dominant immune cell populations. Using multiple mechanisms, lipoprotein-derived components activate both the innate and adaptive immune systems. Cholesterol crystals and apolipoprotein B-peptides have been shown to activate macrophages and T cells, respectively. Lipoproteins are also important modulators of regulatory T cells that can hamper vascular inflammation. In the liver, T cells can influence hepatic inflammation and lipoprotein metabolism. Hence, there is an intricate crosstalk between the immune system and lipoprotein metabolism.
Novel treatments are needed to prevent clinical manifestations of atherosclerosis. Improved understanding of lipid-driven immunometabolic responses is likely to reveal new therapeutic targets.
动脉粥样硬化是一种慢性炎症性疾病，其中脂蛋白在内皮下的浸润导致动脉炎症病变。尽管二级预防有所改善，但目前的治疗方法仍无法避免大多数心血管事件。本综述重点介绍了脂质驱动的免疫激活的新机制见解，这为动脉粥样硬化的新抗炎治疗铺平了道路。
免疫代谢相互作用可以塑造免疫反应。在动脉粥样硬化斑块中，巨噬细胞和 T 细胞是主要的免疫细胞群体。脂蛋白衍生成分通过多种机制激活先天和适应性免疫系统。胆固醇晶体和载脂蛋白 B 肽已被证明分别激活巨噬细胞和 T 细胞。脂蛋白也是调节性 T 细胞的重要调节剂，可阻碍血管炎症。在肝脏中，T 细胞可以影响肝脏炎症和脂蛋白代谢。因此，免疫系统和脂蛋白代谢之间存在着复杂的相互作用。
需要新的治疗方法来预防动脉粥样硬化的临床表现。对脂质驱动的免疫代谢反应的深入了解可能会揭示新的治疗靶点。
