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MicroRNA-1185 Promotes Arterial Stiffness though Modulating VCAM-1 and E-Selectin Expression

Haoyuan Deng, Zhenfeng Song, Huan Xu, Xinrui Deng, Qiao Zhang, Hongyu Chen, Yanjiao Wang, Ying Qin, Ying Li
2017 Cellular Physiology and Biochemistry  
Background/Aims: Atherosclerosis is the primary cause of cardiovascular ischaemic events; arterial stiffness is a characteristic of the atherosclerotic process. MicroRNAs (miRNAs) have been revealed as crucial modulators of atherosclerosis. However, the role of arterial stiffnessrelated miRNAs in the atherosclerotic process is still unclear. Methods: Four hundred six participants from Northern China were enrolled in this study. Circulating miR-1185 and adhesion molecule levels were measured.
more » ... s were measured. Multiple linear regression models were used to evaluate the association of miR-1185 levels with brachial-ankle pulse wave velocity (baPWV) and adhesion molecule levels. A mediation analysis was also performed to examine the mediating effect. Cell adhesion molecule levels were measured in primary human umbilical vein endothelial cells (pHUVECs) and human umbilical vein smooth cells (HUVSMCs) transfected with miR-1185 or co-transfected with a miR-1185 inhibitor. Results: miR-1185 was independently correlated with arterial stiffness. A positive relationship between miR-1185 and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels was observed. VCAM-1 and E-selectin partially mediated the correlation between miR-1185 and arterial stiffness. miR-1185 induced a significant increase in the VCAM-1 and E-selectin levels in pHUVECs and HUVSMCs in vitro. According to our mechanistic analysis, VCAM-1 and E-selectin mediated miR-1185-induced arterial stiffening. Conclusions: miR-1185 modulated the expression of VCAM-1 and E-selectin to promote arterial stiffening, suggesting that miR-1185 plays a crucial role in the development of atherosclerosis and may serve as a novel therapeutic target for atherosclerosis. and E-selectin in the model. The β1 to β4 values were used to calculate the overall indirect effects of VCAM-1 and E-selectin, respectively (β ind = 0.025 for VCAM-1 and β ind = 0.035 for E-selectin; both P < 0.05). The percentages of the total effects mediated by VCAM-1 and E-selectin were estimated to be 8.80% and 12.32% (both P < 0.05).
doi:10.1159/000475576 pmid:28441665 fatcat:ckcg7fjpb5hqpkzdma5xkppukq