Biomaterial Surface Can Modify HUVEC Morphology and Inflammatory Response by Regulating MicroRNA Expression

Vascular inflammation is an important process which contributes to the pathogenesis of many cardiovascular diseases, such as atherosclerosis. MicroRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Prior researches had shown that alterations in gene expression of human umbilical vein endothelial cells (HUVECs) associated with topo-graphic cues. Here, we showed that poly (dimethyl siloxane) (PDMS) substrate of 10 μm width and 3 μm depth parallel microgrooves on the surface could significantly upregulate the expression of anti-inflammatory microRNAs, miR-146a and miR-181b. In addition, the results also showed that TRAF6 and importin-α3, target of miR-146a and miR-181b, respectively, were both down-regulated (P < 0.05 and P < 0.001, respectively). The expression levels of the inflammation related proteins were all significantly decreased, including VCAM-1 (P < 0.05), ICAM-1 (P < 0.001), E-selectin (P < 0.001), and MCP-1 (P < 0.05). The adhesion of the mononuclear cell line, THP-1, was significantly decreased (P < 0.05). The results revealed that morphology modified HUVEC can modulate miR-146a and miR-181b and their downstream biological functions such as decreasing inflammation, suggesting that surface microtopology may affect vascular inflammation in the setting of cardiovascular disease. These interesting findings will facilitate the optimal design of microstructured materials in tissue engineering.