Inhibition of miR-29b suppresses MAPK signaling pathway through targeting SPRY1 in atherosclerosis.

The treatment of atherosclerosis (AS), a severe condition associated with the pathogenesis of cardiovascular diseases (CVDs), is still not satisfactory worldwide. In this study, we aim to investigate whether protein sprout homologue 1 (SPRY1), a upstream mediator of MAPK signal pathway, is the target of miR-29b in vascular endothelium during the development of AS. ApoE-/- mice model was established, and an inverse correlation was noticed between level of miR-29b and SPRY1 expression in the aortic tissues. Meanwhile, the tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) expression and NADPH oxidase activity were up-regulated in atherosclerotic tissues. In vitro experiments were carried out to investigate the roles of miR-29b in regulating the expression of SPRY1 in cultured human umbilical vein endothelial cells (HUVECs). We found that miR-29b mimic and antagomir could modulate the expression of SPRY1 protein in cultured HUVECs. However, the expression of SPRY1 mRNA showed no statistical difference when treating with miR-29b mimic or antagomir. These indicated that the modulation of SPRY1 induced by miR-29b was at the posttranslational level. Dural luciferase reporter assay was conducted to detect the potential interaction between miR-29b and the 3'UTR of SPRY1, which indicated that SPRY1 was a target of miR-29b. Besides, miR-29b antagomir induced decrease of TNF-α, ROS production and NADPH oxidase activity and down-regulated the expression of p-ERK and p-p38 in the presence of oxLDL. In conclusion, inhibition of miR-29b could attenuate AS by inhibiting the SPRY1/MAPK signaling pathway and inflammation in aorta. In future, treatment options based on miR-29b may be applicable for the treatment of AS.