Monocyte-Derived miRNA-1914-5p Attenuates IL-1ß-Induced Monocyte Adhesion and Transmigration.

Atherosclerosis can lead to cardiovascular and cerebrovascular diseases. Atherosclerotic plaque formation is promoted by the accumulation of inflammatory cells. Therefore, modulating monocyte recruitment represents a potential therapeutic strategy. In an inflammatory state, the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) is upregulated in endothelial cells. We previously reported that miR-1914-5p in endothelial cells suppresses interleukin (IL)-1ß-induced ICAM-1 expression and monocyte adhesion to endothelial cells. However, whether monocyte miR-1914-5p affects monocyte recruitment is unclear. In this study, IL-1ß decreased miR-1914-5p expression in a human monocyte cell line. Moreover, miR-1914-5p inhibition enhanced adhesion to endothelial cells with the upregulation of macrophage-1 antigen (Mac-1), a counter-ligand to ICAM-1. Transmigration through the endothelial layer was also promoted with the upregulation of monocyte chemotactic protein-1 (MCP-1). Furthermore, a miR-1914-5p mimic suppressed IL-1ß-induced monocyte adhesion and transmigration in monocytes with Mac-1 and MCP-1 downregulation. Further investigation of miR-1914-5p in monocytes could lead to the development of novel diagnostic markers and therapeutic strategies for atherosclerosis.

Interleukin-1ß enhances cell adhesion in human endothelial cells via microRNA-1914-5p suppression.

Atherosclerosis is a chronic inflammatory disease and the underlying cause of most cardiovascular diseases. Interleukin (IL)-1ß facilitates early atherogenic lesion formation by increasing monocyte adhesion to endothelial cells via upregulation of adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1). MicroRNAs (miRNAs) have been shown to be associated with inflammatory conditions in the vascular system. The expression of circulating miR-1914-5p is reportedly downregulated in patients with cardiovascular diseases. However, the role of miR-1914-5p downregulation in IL-1ß-induced endothelial cell dysfunction and the effect of miR-1914-5p on lesion formation remain unclear. Therefore, we investigated whether miR-1914-5p is associated with monocyte adhesion in human endothelial cells. IL-1ß decreased miR-1914-5p expression in EA.hy926 cells. In addition, miR-1914-5p depletion enhanced ICAM-1 expression and monocyte adhesion in EA.hy926 cells. Moreover, miR-1914-5p mimic suppressed monocyte adhesion and ICAM-1 expression induced by IL-1ß in endothelial cells. These results suggest that suppression of miR-1914-5p expression by IL-1ß may be an important regulator in mediating monocyte adhesion in endothelial cells. Further investigation of miR-1914-5p may lead to the development of novel therapeutic strategies for atherosclerosis.

IL-6 promotes cell adhesion in human endothelial cells via microRNA-126-3p suppression.

Atherosclerosis is an important underlying cause of cardiovascular diseases; vascular endothelial cells play a vital role in inflammatory responses in the initial steps of atherosclerosis. High levels of the pro-inflammatory cytokine interleukin-6 (IL-6) long have been considered a risk factor in the development and complications of atherosclerotic disease. However, it is still controversial whether IL-6 is atherogenic or atheroprotective. Recently, miR-126-3p, an endothelial cell-specific microRNA, has been proposed as an atheroprotective molecule. Therefore, we investigated whether IL-6 accelerates endothelial cell responses through the suppression of miR-126-3p expression in human endothelial cell line EA.hy926. IL-6 yielded concentration-dependent decreases in miRNA-126-3p accumulation in EA.hy926 cells, leading in turn to increased expression of genes targeted by miRNA-126-3p. In addition, adhesion of the human monocyte cell line THP-1 was enhanced by the exposure of EA.hy926 cells to IL-6, with associated increases in the levels of the adhesion molecule intercellular adhesion molecule-1 (ICAM-1). Suppression of miR-126-3p expression resulted in upregulation of miRNA-126-3p-regulated genes, enhanced adhesion of THP-1 cells, and increased ICAM-1 accumulation in EA.hy926 cells. In contrast, miR-126-3p overproduction had the opposite effects. The regulation of miRNA-126-3p by IL-6 may have important implications for the development of novel protective therapies targeting atherosclerosis.