Endothelial Cell Morphology Regulates Inflammatory Cells Through MicroRNA Transferred by Extracellular Vesicles

Abstract

Vascular inflammation plays an important role in the pathogenesis and the development of cardiovascular diseases such as arteriosclerosis and restenosis, and the dysfunction of endothelial cells (ECs) may result in the activation of monocytes and other inflammatory cells. ECs exhibit an elongated morphology in the straight part of arteries but a cobblestone shape near the pro-atherogenic region such as branch bifurcation. Although the effects of hemodynamic forces on ECs have been widely studied, it is not clear whether the EC morphology affects its own function and thus the inflammatory response of monocytes. Here we showed that elongated ECs cultured on poly-(dimethyl siloxane) membrane surface with microgrooves significantly suppressed the activation of the monocytes in co-culture, in comparison to ECs with a cobblestone shape. The transfer of EC-conditioned medium to monocytes had the same effect, suggesting that soluble factors were involved in EC-monocyte communication. Further investigation demonstrated that elongated ECs upregulated the expression of anti-inflammatory microRNAs, especially miR-10a. Moreover, miR-10a was found in the extracellular vesicles (EVs) released by ECs and transferred to monocytes, and the inhibition of EV secretion from ECs repressed the upregulation of miR-10a. Consistently, the inhibition of miR-10a expression in ECs reduced their anti-inflammatory effect on monocytes. These results reveal that the EC morphology can regulate inflammatory response through EVs, which provides a basis for the design and the optimization of biomaterials for vascular tissue engineering.

Lipid Metabolism Disorders in the Comorbid Course of Nonalcoholic Fatty Liver Disease and Chronic Obstructive Pulmonary Disease

“…The ability to generate microparticles is known for various cell types, including endothelial and myeloid cells [ 222 , 223 , 224 ]. Microparticles are now considered part of a complex mechanism of intercellular interaction and information exchange through the transfer of microRNAs and some proteins, including those thought to have functional activity [ 225 , 226 ]. Microparticles can be taken up by other cells and thus gain a biological link to the original cell.…”

Extracellular vesicle microRNA cargoes from intermittent hypoxia-exposed cardiomyocytes and their effect on endothelium

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Endothelial Extracellular Vesicles: From Keepers of Health to Messengers of Disease

“…These studies are essential first steps to characterizing EVs derived from a specific cell line and their impacts on a defined recipient cell type, as current in vivo approaches are challenging due to the multiple cellular sources of EVs that may lack specific markers, tracking difficulties and complex biodistributions. The importance of physiological conditions was demonstrated when HUVECS were cultured on a poly-dimethyl siloxane membrane to create elongated endothelial cells, and it showed that EVs expressed from elongated endothelial cells suppressed the activation of monocytes via the upregulation of anti-inflammatory miRNAs [ 143 ]. When considering 2D and 3D models, it was demonstrated that 3D models better mimic in-vivo EV characteristics of size distribution and cargo [ 144 ].…”