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Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
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.
Abstract:
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.
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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