Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis.
Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis.
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DOI：
10.1371/journal.pone.0185406
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Tong W
中科院分区：
文献类型：
--
作者：
Chen L;Yang W;Guo Y;Chen W;Zheng P;Zeng J;Tong W
动脉粥样硬化是一种由脂质引起的血管壁慢性炎症。氧化低密度脂蛋白（oxLDL）驱动涉及巨噬细胞和内皮细胞（EC）的动脉粥样硬化形成的开始。我们早期的工作表明，在从患者和动物模型收集的动脉粥样硬化斑块中，长非编码RNA生长抑制特异性5（lncRNA GAS 5）的表达显著增加。在这项研究中，我们发现lncRNA GAS 5的敲低减少了oxLDL处理的THP-1细胞的凋亡。与此相反，lncRNAGAS 5的过表达显著增加了oxLDL刺激后THP-1细胞的凋亡。Caspase等凋亡因子的表达随lncRNAGAS 5水平的变化而变化。此外，lncRNA GAS 5在oxLDL刺激后在THP-1衍生的外泌体中被发现。来源于lncRNA GAS 5过表达的THP-1细胞的外泌体在摄取这些外泌体后增强了血管内皮细胞的凋亡。然而，由lncRNA GAS 5敲低的THP-1细胞脱落的exosomes抑制内皮细胞的凋亡。这些发现揭示了lncRNA GAS 5在动脉粥样硬化形成中的作用，其通过exosomes调节巨噬细胞和内皮细胞的凋亡，并提示抑制lncRNA GAS 5可能是治疗动脉粥样硬化的有效途径。
Atherosclerosis is universally recognized as a chronic lipid-induced inflammation of the vessel wall. Oxidized low density lipoprotein (oxLDL) drives the onset of atherogenesis involving macrophages and endothelial cells (ECs). Our earlier work showed that expression of long noncoding RNA-growth arrest-specific 5 (lncRNA GAS5) was significantly increased in the plaque of atherosclerosis collected from patients and animal models. In this study, we found that knockdown of lncRNA GAS5 reduced the apoptosis of THP-1 cells treated with oxLDL. On the contrary, overexpression of lncRNA GAS5 significantly elevated the apoptosis of THP-1 cells after oxLDL stimulation. The expressions of apoptotic factors including Caspases were changed with lncRNA GAS5 levels. Moreover, lncRNA GAS5 was found in THP-1 derived-exosomes after oxLDL stimulation. Exosomes derived from lncRNA GAS5-overexpressing THP-1 cells enhanced the apoptosis of vascular endothelial cells after taking up these exosomes. However, exosomes shed by lncRNA GAS5 knocked-down THP-1 cells inhibited the apoptosis of endothelial cells. These findings reveal the function of lncRNA GAS5 in atherogenesis which regulates the apoptosis of macrophages and endothelial cells via exosomes and suggest that suppressing the lncRNA GAS5 might be an effective way for the therapy of atherosclerosis.
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