Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes.
Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes.
复制标题
DOI：
10.1016/j.bbrc.2009.06.095
复制
发表时间：
2009-09
影响因子：
3.1
通讯作者：
R. Zhan;Xue Leng;Xiaohua Liu;Xinxing Wang;J. Gong;Li-Cheng Yan;Liqun Wang;Yang Wang;
中科院分区：
文献类型：
--
作者：
R. Zhan;Xue Leng;Xiaohua Liu;Xinxing Wang;J. Gong;Li-Cheng Yan;Liqun Wang;Yang Wang;
新出现的证据表明，高水平的循环热休克蛋白70（HSP 70）与血管疾病的风险较低相关;然而，这种反向关系的生物学意义尚未探讨。在此，我们报告氧化低密度脂蛋白（Ox-LDL）和同型半胱氨酸（Hcy）诱导内皮细胞HSP 70的释放。在大鼠内皮细胞中，Ox-LDL和Hcy诱导HSP 70的稳健释放，独立于内质网/高尔基体蛋白运输或脂筏形成的经典途径。而Ox-LDL和Hcy则显著促进了外泌体的分泌，并增加了外泌体中HSP 70的含量。外源性HSP 70对LPS、Ox-LDL和Hcy诱导的内皮细胞活化没有影响，而HSP 70单独激活单核细胞，导致单核细胞粘附于内皮细胞。这些结果表明，外泌体依赖性分泌的HSP 70从内皮细胞提供了一种新的旁分泌机制，以调节血管内皮功能的完整性。
Emerging evidence suggests that a high level of circulating heat shock protein 70 (HSP70) correlates with a lower risk of vascular disease; however, the biological significance of this inverse relationship has not been explored. Herein, we report that oxidative low density lipoprotein (Ox-LDL) and homocysteine (Hcy) induce HSP70 release from endothelial cells. In rat endothelial cells, Ox-LDL and Hcy induced robust release of HSP70, independent of the classical route of endoplasmic reticulum/Golgi protein trafficking or the formation of lipid rafts. In contrast, Ox-LDL and Hcy significantly enhanced the exosomal secretory rate and increased the HSP70 content of exosomes. Exogenous HSP70 had no impact on LPS-, Ox-LDL- and Hcy-induced activation of endothelial cells, whereas HSP70 did activate monocytes alone, resulting in monocyte adhesion to endothelial cells. These results indicate that exosome-dependent secretion of HSP70 from endothelial cells provides a novel paracrine mechanism to regulate vascular endothelial functional integrity.