Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI
Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI
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溶血磷脂酸通过阻断 SRBI 的表达直接诱导巨噬细胞来源的泡沫细胞形成
DOI：
10.1016/j.bbrc.2017.07.159
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发表时间：
2017-09-23
影响因子：
3.1
通讯作者：
Yu, Chao
中科院分区：
文献类型：
--
作者：
Chen, Linmu;Zhang, Jun;Yu, Chao
发病率和死亡率的主要原因是心血管疾病的结果，主要是动脉粥样硬化。巨噬细胞泡沫细胞的形成和内皮下空间的局灶性滞留是早期动脉粥样硬化病变的标志。溶血磷脂酸（LPA）是一种富含氧化LDL的低分子量溶血磷脂，对心血管系统有一系列影响。以往的研究表明，LPA可增加ox-LDL的摄取，促进泡沫细胞的形成。然而，作为ox-LDL中最具活性的成分，LPA是否直接影响泡沫细胞的形成还未见报道。本研究的目的是研究LPA对泡沫细胞形成的影响，以及阐明其潜在的机制。油红0染色和胆固醇/胆固醇酯定量测定用于评价Raw 264.7巨噬细胞中的泡沫细胞形成。我们利用Western blot和RT-PCR技术研究LPA受体与脂质转运相关蛋白的关系。我们发现，LPA促进泡沫细胞的形成，使用200 μ M 24小时。同时，促进游离胆固醇流出的清道夫受体BI（SRBI）的表达降低。LPA（1/3）受体拮抗剂Ki 16425可显著阻断LPA的作用，提示LPA（1/3）参与了LPA诱导的泡沫细胞形成和SRBI表达。此外，用AKT抑制剂阻断LPA诱导的泡沫细胞形成。我们的研究结果表明，LPA增强的泡沫细胞形成介导的LP 1/3 -AKT激活和随后的SRBI表达。(C)2017由Elsevier Inc.出版
The leading cause of morbidity and mortality is the result of cardiovascular disease, mainly atherosclerosis. The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the sub endothelial space are the hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a range of effects on the cardiovascular system. Previous reports show that LPA increases the uptake of ox-LDL to promote the formation of foam cells. However, as the most active component of ox-LDL, there is no report showing whether LPA directly affects foam cell formation. The aim of this study was to investigate the effects of LPA on foam cell formation, as well as to elucidate the underlying mechanism. Oil red 0 staining and a Cholesterol/cholesteryl ester quantitation assay were used to evaluate foam cell formation in Raw264.7 macrophage cells. We utilized a Western blot and RT-PCR to investigate the relationship between LPA receptors and lipid transport related proteins. We found that LPA promoted foam cell formation, using 200 mu M for 24 h. Meanwhile, the expression of the Scavenger receptor BI (SRBI), which promotes the efflux of free cholesterol, was decreased. Furthermore, the LPA(1/3) receptor antagonist Ki16425 significantly abolished the LPA effects, indicating that LPA(1/3) was involved in the foam cell formation and SRBI expression induced by LPA. Additionally, the LPA-induced foam cell formation was blocked with an AKT inhibitor. Our results suggest that LPA-enhanced foam cell formation is mediated by LP1/3 -AKT activation and subsequent SRBI expression. (C) 2017 Published by Elsevier Inc.