Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.

动脉粥样硬化是动脉壁的慢性炎症性疾病，循环单核细胞与内皮细胞的粘附是动脉粥样硬化发病机制中至关重要的一步。上皮-间质相互作用 1 (EPSTI1) 是一种新基因，在人类乳腺癌中由上皮-间质相互作用显着诱导。EPSTI1的表达不仅限于乳腺，也在其他正常组织中表达。在这项研究中，我们研究了 EPSTI1 在单核细胞-内皮细胞粘附中的作用及其在动脉粥样硬化斑块中的表达模式。我们发现，与正常动脉相比，EPSTI1 在人类和小鼠动脉粥样硬化斑块中显着上调。此外，人和小鼠动脉粥样硬化斑块内皮细胞中EPSTI1的表达量显着高于正常动脉。此外，我们证明 EPSTI1 通过上调 HUVEC 中 VCAM-1 和 ICAM-1 的表达来促进人单核 THP-1 细胞与人脐静脉内皮细胞 (HUVEC) 的粘附。LPS（100、500、1000 ng/mL）处理以剂量和时间依赖性方式诱导 HUVEC 在 mRNA 和蛋白质水平上表达 EPSTI1。EPSTI1 的敲低通过下调 VCAM-1 和 ICAM-1 显着抑制 LPS 诱导的单核细胞 - 内皮细胞粘附。此外，我们发现 LPS 通过 p65 核转位诱导 EPSTI1 表达。因此，我们得出结论，EPSTI1通过上调VCAM-1和ICAM-1的表达来促进THP-1细胞与内皮细胞的粘附，这意味着它在动脉粥样硬化的发展中具有潜在的作用。