MiR-181b Antagonizes Atherosclerotic Plaque Vulnerability By Modulating Macrophage Polarization Through Directly Targeting Notch1

In acute stroke patients with atherosclerotic plaque, we found that the serum level of miR-181 b was decreased. 8 w Apolipoprotein E knock-out(ApoE-/-) mice were randomly divided into three groups(N=10): mice fed with normal diet and tail vein injection with normal saline(Ctrl), mice fed with high fat diet and tail vein injection with miR-181 b agomir negative control(AG-NC) and miR-181 b agomir(181b-AG). We found the serum level of miR-181 b in AG-NC group was lower than Ctrl group too. Moreover, 181b-AG could reduce artery burden, and attenuate atherosclerotic plaque vulnerability by modulating macrophage polarization in atherosclerotic plaque. In RAW264.7 cells treated with ox-LDL(oxidized low-density lipoprotein), we found that miR-181 b could increase M2 markers and decrease M1 markers at both mRNA and protein levels. Furthermore, we found that Notch1 could be regulated by miR-181 b in vivo and in vitro, and may be a direct target of miR-181 b. Finally, pharmacological inhibition of Notch1 could partly abolish miR-181b's function of increasing M2 phenotype. Collectively,our study demonstrates that administration of miR-181 b could reduce atherosclerotic plaque vulnerability partly through modulating macrophage phenotype, and Notch1 maybe the possible target.