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

Li Chen1, Liqun Hu1, Xiang Zhu1

  • 1Department of Gerontology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China; Anhui Provincial Hospital, Anhui Medical University , Hefei Anhui, 230001, P.R.China.

Insights

This study reveals MALAT1 inhibits oxidized LDL-induced dendritic cell maturation in atherosclerosis. Overexpressing MALAT1 reduces atherosclerotic plaque by regulating the miR-155-5p/NFIA axis, offering a potential treatment strategy for atherosclerosis.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cardiovascular Research

Background:

  • Atherosclerosis (AS) involves dendritic cells (DCs) maturation.
  • The role of MALAT1 in AS-related DC maturation requires clarification.

Purpose of the Study:

  • To investigate the function of MALAT1 in oxidized low-density lipoprotein (ox-LDL)-induced DC maturation in AS.
  • To elucidate the regulatory mechanism of MALAT1 in AS.

Main Methods:

  • Immature DCs (iDCs) from healthy volunteers or ApoE-/- mice were treated with ox-LDL.
  • MALAT1, NFIA, and miR-155-5p levels were analyzed.
  • DC maturation markers (CD83, CD86, IL-12, IL-6) were assessed.
  • In vivo studies in AS mice were conducted.

Main Results:

  • Ox-LDL promoted DC maturation markers and upregulated miR-155-5p while downregulating MALAT1 and NFIA.
  • MALAT1 overexpression suppressed ox-LDL-induced DC maturation.
  • MALAT1 acts as a competing endogenous RNA for miR-155-5p, targeting NFIA.
  • MALAT1 overexpression reduced atherosclerotic plaque area in AS mice.

Conclusions:

  • MALAT1 overexpression attenuates AS by inhibiting ox-LDL-stimulated DC maturation via the miR-155-5p/NFIA axis.
  • The MALAT1/miR-155-5p/NFIA axis presents a potential therapeutic target for AS treatment.

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