Lipid droplet-associated proteins in atherosclerosis (Review).
Lipid droplet-associated proteins in atherosclerosis (Review).
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DOI：
10.3892/mmr.2016.5099
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发表时间：
2016-06
影响因子：
3.4
通讯作者：
Goo YH
中科院分区：
文献类型：
--
作者：
Plakkal Ayyappan J;Paul A;Goo YH
动脉壁内动脉粥样硬化斑块的积聚会导致严重的心血管疾病和中风。巨噬细胞/泡沫细胞是动脉粥样硬化斑块的中心成分，它填充在动脉壁上，以清除有害的修饰低密度脂蛋白(LDL)颗粒，导致脂质(主要是低密度脂蛋白衍生的胆固醇酯)在胞浆脂滴(LDs)中积聚。目前，LDS被认为是控制细胞代谢过程的动态细胞器。LD由中性脂的内核组成，被磷脂和游离胆固醇的单层包围，并含有调节LD功能的LD相关蛋白(LDAP)。泡沫细胞的特点是胞浆内LDs异常堆积，在发育的所有阶段都被认为是动脉粥样硬化病变的标志。以前的研究已经探讨了泡沫细胞形成的机制，旨在发现以泡沫细胞为靶点并干预动脉粥样硬化的治疗策略。众所周知，LDAP在脂代谢紊乱引起的代谢性疾病的发病机制中起着重要作用，一些研究已将LDAP与动脉粥样硬化的发展联系起来。在这篇综述中，描述了几种泡沫细胞靶向途径，重点是LDAP在巨噬细胞胆固醇动员中的作用。此外，还讨论了LDAP作为治疗靶点预防疾病进展和/或促进疾病消退的潜力。
Accumulation of atherosclerotic plaques in arterial walls leads to major cardiovascular diseases and stroke. Macrophages/foam cells are central components of atherosclerotic plaques, which populate the arterial wall in order to remove harmful modified low-density lipoprotein (LDL) particles, resulting in the accumulation of lipids, mostly LDL-derived cholesterol ester, in cytosolic lipid droplets (LDs). At present, LDs are recognized as dynamic organelles that govern cellular metabolic processes. LDs consist of an inner core of neutral lipids surrounded by a monolayer of phospholipids and free cholesterol, and contain LD-associated proteins (LDAPs) that regulate LD functions. Foam cells are characterized by an aberrant accumulation of cytosolic LDs, and are considered a hallmark of atherosclerotic lesions through all stages of development. Previous studies have investigated the mechanisms underlying foam cell formation, aiming to discover therapeutic strategies that target foam cells and intervene against atherosclerosis. It is well established that LDAPs have a major role in the pathogenesis of metabolic diseases caused by dysfunction of lipid metabolism, and several studies have linked LDAPs to the development of atherosclerosis. In this review, several foam cell-targeting pathways have been described, with an emphasis on the role of LDAPs in cholesterol mobilization from macrophages. In addition, the potential of LDAPs as therapeutic targets to prevent the progression and/or facilitate the regression of the disease has been discussed.