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Extracellular traps from activated vascular smooth muscle cells drive the progression of atherosclerosis

Author

Listed:
  • Ming Zhai

    (School of Medicine)

  • Shiyu Gong

    (School of Medicine)

  • Peipei Luan

    (School of Medicine)

  • Yefei Shi

    (School of Medicine)

  • Wenxin Kou

    (School of Medicine)

  • Yanxi Zeng

    (School of Medicine)

  • Jiayun Shi

    (School of Medicine)

  • Guanye Yu

    (School of Medicine)

  • Jiayun Hou

    (Fudan University)

  • Qing Yu

    (School of Medicine)

  • Weixia Jian

    (School of Medicine)

  • Jianhui Zhuang

    (School of Medicine)

  • Mark W. Feinberg

    (Harvard Medical School)

  • Wenhui Peng

    (School of Medicine)

Abstract

Extracellular DNA traps (ETs) represent an immune response by which cells release essential materials like chromatin and granular proteins. Previous studies have demonstrated that the transdifferentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. This study seeks to investigate the interaction between CD68+ VSMCs and the formation of ETs and highlight its function in atherosclerosis. Here we show that ETs are inhibited, and atherosclerotic plaque formation is alleviated in male Myh11CrePad4flox/flox mice undergoing an adeno-associated-virus-8 (AAV8) mediating overexpression of proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) injection and being challenged with a high-fat diet. Obvious ETs generated from CD68+ VSMCs are inhibited by Cl-amidine and DNase I in vitro. By utilizing VSMCs-lineage tracing technology and single-cell RNA sequencing (scRNA-seq), we demonstrate that the ETs from CD68+ VSMCs influence the progress of atherosclerosis by regulating the direction of VSMCs’ transdifferentiation through STING-SOCS1 or TLR4 signaling pathway.

Suggested Citation

  • Ming Zhai & Shiyu Gong & Peipei Luan & Yefei Shi & Wenxin Kou & Yanxi Zeng & Jiayun Shi & Guanye Yu & Jiayun Hou & Qing Yu & Weixia Jian & Jianhui Zhuang & Mark W. Feinberg & Wenhui Peng, 2022. "Extracellular traps from activated vascular smooth muscle cells drive the progression of atherosclerosis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35330-1
    DOI: 10.1038/s41467-022-35330-1
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    References listed on IDEAS

    as
    1. Yuan Guan & Annika Enejder & Meiyue Wang & Zhuoqing Fang & Lu Cui & Shih-Yu Chen & Jingxiao Wang & Yalun Tan & Manhong Wu & Xinyu Chen & Patrik K. Johansson & Issra Osman & Koshi Kunimoto & Pierre Rus, 2021. "A human multi-lineage hepatic organoid model for liver fibrosis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
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