Hajjar David P, Hajjar Katherine A
Department of Biochemistry and Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, USA.
Department of Pediatrics and Department of Cell and Developmental Biology, Weill Cornell Medicine, Cornell University, New York, USA.
J Enzymol Metab. 2016;1(1). Epub 2016 May 31.
Vascular inflammation is central to the pathogenesis of the atherosclerotic lesion. In the setting of hypercholesterolemia, vascular inflammation accelerates the accumulation of cholesterol within arterial smooth muscle cells, macrophages, and other immune cells. In disorders such as obesity, diabetes, and thrombosis, a myriad of interactions between sterol metabolites and inflammatory mediators exacerbate cholesterol deposition in the vessel wall, leading to the well-known consequences of stroke, transient ischemic attack, myocardial infarction, and peripheral vascular insufficiency. This review highlights emerging concepts in the regulation of cholesterol synthesis, the lipolytic enzymes involved in cholesterol utilization, and the therapies that successfully modulate vascular inflammation. In addition, developments relating to the role of inflammasomes in the management of cholesterol-mediated inflammation are discussed.
血管炎症是动脉粥样硬化病变发病机制的核心。在高胆固醇血症的情况下,血管炎症会加速胆固醇在动脉平滑肌细胞、巨噬细胞和其他免疫细胞内的蓄积。在肥胖、糖尿病和血栓形成等病症中,甾醇代谢产物与炎症介质之间的无数相互作用会加剧胆固醇在血管壁的沉积,从而导致中风、短暂性脑缺血发作、心肌梗死和外周血管功能不全等众所周知的后果。本综述重点介绍了胆固醇合成调节、参与胆固醇利用的脂解酶以及成功调节血管炎症的疗法等方面的新观念。此外,还讨论了炎性小体在胆固醇介导的炎症管理中的作用相关进展。