Intermittent hypoxia increased the expression of ESM1 and ICAM-1 in vascular endothelial cells via the downregulation of microRNA-181a1.

Abstract

Sleep apnea syndrome (SAS) exposes cells throughout the body to intermittent hypoxia (IH). Intermittent hypoxia is a risk factor not only for hypertension and insulin resistance but also for vascular dysfunction. We have reported correlations between IH, insulin resistance and hypertension. However, the details of why IH leads to vascular dysfunction remain unclear. In this study, we investigated inflammation-related transcripts in vascular endothelial cells (human HUEhT-1 and mouse UV2) exposed to IH by real-time RT-PCR and found that intercellular adhesion molecule-1 (ICAM-1) and endothelial cell-specific molecule-1 (ESM1) mRNAs were significantly increased. ELISA confirmed that, in the UV2 cell medium, ICAM-1 and ESM1 were significantly increased by IH. However, the promoter activities of ICAM-1 and ESM1 were not upregulated. On the other hand, IH treatment significantly decreased microRNA (miR)-181a1 in IH-treated cells. The introduction of miR-181a1 mimic but not miR-181a1 mimic NC abolished the IH-induced upregulation of Ican-1 and ESM1. These results indicated that ICAM-1 and ESM1 were upregulated by IH via the IH-induced downregulation of miR-181a1 in vascular endothelial cells and suggested that SAS patients developed atherosclerosis via the IH-induced upregulation of ICAM-1 and ESM1.

• Authors: Shin Takasawa, Mai Makino, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Rina Hirota, Ryusei Fujii, Keito Asai, Yoshinori Takeda, Tomoko Uchiyama, Ryogo Shobatake, Hiroyo Ota
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) (Nov 15 2023) ISSN: 1582-4934 [Electronic] England
• PMID: 37968862 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.