Alterations of Cholesterol Metabolism in Inflammation-Induced Atherogenesis.

Journal of enzymology and metabolism Pub Date : 2016-01-01 Epub Date: 2016-05-31
David P Hajjar, Katherine A Hajjar
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Abstract

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.

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炎症诱导的动脉粥样硬化中胆固醇代谢的改变。
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,血管炎症加速了动脉平滑肌细胞、巨噬细胞和其他免疫细胞内胆固醇的积累。在肥胖症、糖尿病和血栓形成等疾病中,胆固醇代谢物和炎症介质之间的多种相互作用加剧了胆固醇在血管壁的沉积,导致中风、短暂性脑缺血发作、心肌梗死和周围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溶酶以及成功调节血管炎症的治疗方法等新兴概念。此外,有关炎症小体在胆固醇介导的炎症管理中的作用的发展进行了讨论。
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