Journal Article

HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells

Barter, Philip J., Prado-Lourenco, Leonel, Catherinet, Claire, Remaley, Alan T., Lambert, Gilles, Shoucri, Bassem M., Tabet, Fatiha, Thacker, Seth, Cuesta Torres, Luisa F., Rye, Kerry-Anne, Sethupathy, Praveen, Vickers, Kasey C., Wiese, Carrie B., Levin, Michael G.

2014

Overview

High-density lipoproteins (HDL) have many biological functions, including reducing endothelial activation and adhesion molecule expression. We recently reported that HDL transport and deliver functional microRNAs (miRNA). Here we show that HDL suppresses expression of intercellular adhesion molecule 1 (ICAM-1) through the transfer of miR-223 to endothelial cells. After incubation of endothelial cells with HDL, mature miR-223 levels are significantly increased in endothelial cells and decreased on HDL. However, miR-223 is not transcribed in endothelial cells and is not increased in cells treated with HDL from miR-223 −/− mice. HDL inhibit ICAM-1 protein levels, but not in cells pretreated with miR-223 inhibitors. ICAM-1 is a direct target of HDL-transferred miR-223 and this is the first example of an extracellular miRNA regulating gene expression in cells where it is not transcribed. Collectively, we demonstrate that HDL’s anti-inflammatory properties are conferred, in part, through HDL-miR-223 delivery and translational repression of ICAM-1 in endothelial cells. Lipoproteins such as HDL can bind and transport microRNAs throughout the body. Here the authors provide a new mechanism contributing to the anti-inflammatory effects of HDL by which HDL-associated miR-223 is transferred to endothelial cells, where it inhibits expression of the adhesion molecule ICAM-1.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/1 / 13/109 / 13/21 / 13/31 / 13/39 / 13/95 / 14 / 14/34 / 38 / 38/39 / 38/61 / 38/70 / 38/77 / 38/88 / 38/90 / 631/208/200 / 631/337/384/331 / 692/699/75 / 82/16 / 82/29 / 82/80 / Adhesion / Adult / Animals / Coronary Vessels - cytology / Coronary Vessels - metabolism / Endothelial Cells - metabolism / Female / Gene Expression / Gene Expression Regulation / Healthy Volunteers / Human Umbilical Vein Endothelial Cells / Humanities and Social Sciences / Humans / Intercellular Adhesion Molecule-1 - metabolism / Lipoproteins, HDL - metabolism / Male / Mice, Inbred C57BL / MicroRNAs - metabolism / multidisciplinary / Science / Science (multidisciplinary)