ESM-1 promotes adhesion between monocytes and endothelial cells under intermittent hypoxia |
| |
Authors: | Haili Sun Huina Zhang Kun Li Hao Wu Xiaojun Zhan Fang Fang Yanwen Qin Yongxiang Wei |
| |
Institution: | 1. Department of Otolaryngology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China;2. The Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China |
| |
Abstract: | Intermittent hypoxia (IH), the key property of obstructive sleep apnea (OSA), is closely associated with endothelial dysfunction. Endothelial-cell-specific molecule-1 (ESM-1, Endocan) is a novel, reported molecule linked to endothelial dysfunction. The aim of this study is to evaluate the effect of IH on ESM-1 expression and the role of ESM-1 in endothelial dysfunction. We found that serum concentration of ESM-1, inter-cellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) is significantly higher in patients with OSA than healthy volunteers (p < 0.01). The expression of ESM-1, hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) was significantly increased in human umbilical vein endothelial cells (HUVECs) by treated IH in a time-dependent manner. HIF-1α short hairpin RNA and vascular endothelial growth factor receptor (VEGFR) inhibitor inhibited the expression of ESM-1 in HUVECs. ICAM-1 and VCAM-1 expressions were significantly enhanced under IH status, accompanied by increased monocyte–endothelial cell adhesion rate ( p < 0.001). Accordingly, ESM-1 silencing decreased the expression of ICAM-1 and VCAM-1 in HUVECs, whereas ESM-1 treatment significantly enhanced ICAM-1 expression accompanied by increasing adhesion ability. ESM-1 is significantly upregulated by the HIF-1α/VEGF pathway under IH in endothelial cells, playing a critical role in enhancing adhesion between monocytes and endothelial cells, which might be a potential target for IH-induced endothelial dysfunction. |
| |
Keywords: | adhesion endothelial dysfunction endothelial-cell-specific molecule-1 (ESM-1) intermittent hypoxia (IH) |
|
|