MALAT1 overexpression attenuates AS by inhibiting ox-LDL-stimulated dendritic cell maturation via miR-155-5p/NFIA axis.

MALAT1 is associated with dendritic cells (DCs) maturation in Atherosclerosis (AS). This article aims to demystify the role of MALAT1 in AS. We separated immature DCs (iDCs) from healthy volunteers or ApoE-/- mice. And iDCs were treated with oxidized low density lipoprotein (ox-LDL) to induce DCs maturation. We found that ox-LDL promoted the levels of DCs maturation markers including CD83, CD86, IL-12 and IL-6. MALAT1 and NFIA were down-regulated, whereas miR-155-5p was up-regulated in the ox-LDL-treated iDCs. Furthermore, DCs maturation was notably suppressed by MALAT1 overexpression, NFIA overexpression or miR-155-5p knockdown. Moreover, MALAT1 functioned as a competing endogenous RNA to repress miR-155-5p, which controlled its down-stream target, NFIA. In addition, MALAT1 overexpression inhibited ox-LDL-stimulated DCs maturation by regulating miR-155-5p/NFIA axis. In AS mice, MALAT1 overexpression attenuated ox-LDL-stimulated DCs maturation and reduced atherosclerotic plaque area. In summary, our study demonstrates that MALAT1 overexpression attenuates AS by inhibiting ox-LDL-stimulated DCs maturation via miR-155-5p/NFIA axis. Thus, MALAT1/miR-155-5p/NFIA axis can potentially be used in the treatment of AS.