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LOX-1 清道夫受体及其在血管疾病治疗中的意义。

The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease.

机构信息

Endothelial Cell Biology Unit, Institute of Molecular & Cellular Biology, LIGHT Laboratories, Clarendon Way, Leeds LS2 9JT, UK.

出版信息

Cardiol Res Pract. 2012;2012:632408. doi: 10.1155/2012/632408. Epub 2012 Feb 19.

Abstract

Cardiovascular disease is the leading cause of death. The disease is due to atherosclerosis which is characterized by lipid and fat accumulation in arterial blood vessel walls. A key causative event is the accumulation of oxidised low density lipoprotein particles within vascular cells, and this is mediated by scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is expressed on endothelial, vascular smooth muscle, and lymphoid cells including macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis. LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization pathway. Transgenic animal model studies show that LOX-1 plays a significant role in atherosclerotic plaque initiation and progression. Administration of LOX-1 antibodies in cellular and animal models suggest that such intervention inhibits atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene therapy or small molecule inhibitors would be new ways to address the increasing incidence of vascular disease in many countries.

摘要

心血管疾病是导致死亡的主要原因。该疾病是由动脉血管壁内的脂质和脂肪积聚引起的,称为动脉粥样硬化。一个关键的致病事件是氧化的低密度脂蛋白颗粒在血管细胞内的积聚,这是由清道夫受体介导的。LOX-1 是一种清道夫受体,存在于内皮细胞、血管平滑肌和包括巨噬细胞在内的淋巴样细胞中。LOX-1 与 OxLDL 颗粒的相互作用刺激动脉粥样硬化。LOX-1 通过网格蛋白非依赖性内化途径介导 OxLDL 的内吞作用。转基因动物模型研究表明,LOX-1 在动脉粥样硬化斑块的起始和进展中起重要作用。在细胞和动物模型中给予 LOX-1 抗体表明,这种干预可抑制动脉粥样硬化。使用基因治疗或小分子抑制剂靶向 LOX-1 功能的抗动脉粥样硬化策略将是解决许多国家血管疾病发病率不断上升的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf2/3290926/98effa61bf5f/CRP2012-632408.001.jpg

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