IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33202-2.html
   My bibliography  Save this article

Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia

Author

Listed:
  • Seung Hyun Lee

    (Hanyang University)

  • Nayoung Kim

    (The Catholic University of Korea
    The Catholic University of Korea)

  • Minkyu Kim

    (Hanyang University)

  • Sang-Ho Woo

    (Seoul National University)

  • Inhee Han

    (Hanyang University)

  • Jisu Park

    (Hanyang University)

  • Kyeongdae Kim

    (Hanyang University)

  • Kyu Seong Park

    (Hanyang University)

  • Kibyeong Kim

    (Hanyang University)

  • Dahee Shim

    (Hanyang University)

  • Sang-eun Park

    (Hanyang University)

  • Jing Yu Zhang

    (Hanyang University)

  • Du-Min Go

    (Seoul National University)

  • Dae-Yong Kim

    (Seoul National University)

  • Won Kee Yoon

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Seung-Pyo Lee

    (Seoul National University Hospital, Seoul National University College of Medicine)

  • Jongsuk Chung

    (Samsung Medical Center)

  • Ki-Wook Kim

    (The University of Illinois College of Medicine)

  • Jung Hwan Park

    (Hanyang University College of Medicine)

  • Seung Hyun Lee

    (Yonsei University College of Medicine)

  • Sak Lee

    (Yonsei University College of Medicine)

  • Soo-jin Ann

    (Yonsei University College of Medicine)

  • Sang-Hak Lee

    (Yonsei University College of Medicine)

  • Hyo-Suk Ahn

    (The Catholic University of Korea
    The Catholic University of Korea)

  • Seong Cheol Jeong

    (The Catholic University of Korea)

  • Tae Kyeong Kim

    (Ewha Womans University)

  • Goo Taeg Oh

    (Ewha Womans University)

  • Woong-Yang Park

    (Samsung Medical Center
    Sungkyunkwan University School of Medicine
    Sungkyunkwan University)

  • Hae-Ock Lee

    (The Catholic University of Korea
    The Catholic University of Korea)

  • Jae-Hoon Choi

    (Hanyang University)

Abstract

Valvular inflammation triggered by hyperlipidemia has been considered as an important initial process of aortic valve disease; however, cellular and molecular evidence remains unclear. Here, we assess the relationship between plasma lipids and valvular inflammation, and identify association of low-density lipoprotein with increased valvular lipid and macrophage accumulation. Single-cell RNA sequencing analysis reveals the cellular heterogeneity of leukocytes, valvular interstitial cells, and valvular endothelial cells, and their phenotypic changes during hyperlipidemia leading to recruitment of monocyte-derived MHC-IIhi macrophages. Interestingly, we find activated PPARγ pathway in Cd36+ valvular endothelial cells increased in hyperlipidemic mice, and the conservation of PPARγ activation in non-calcified human aortic valves. While the PPARγ inhibition promotes inflammation, PPARγ activation using pioglitazone reduces valvular inflammation in hyperlipidemic mice. These results show that low-density lipoprotein is the main lipoprotein accumulated in the aortic valve during hyperlipidemia, leading to early-stage aortic valve disease, and PPARγ activation protects the aortic valve against inflammation.

Suggested Citation

  • Seung Hyun Lee & Nayoung Kim & Minkyu Kim & Sang-Ho Woo & Inhee Han & Jisu Park & Kyeongdae Kim & Kyu Seong Park & Kibyeong Kim & Dahee Shim & Sang-eun Park & Jing Yu Zhang & Du-Min Go & Dae-Yong Kim , 2022. "Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33202-2
    DOI: 10.1038/s41467-022-33202-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33202-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-33202-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yongzhong Hou & France Moreau & Kris Chadee, 2012. "PPARγ is an E3 ligase that induces the degradation of NFκB/p65," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    2. Linzhang Huang & Ken L. Chambliss & Xiaofei Gao & Ivan S. Yuhanna & Erica Behling-Kelly & Sonia Bergaya & Mohamed Ahmed & Peter Michaely & Kate Luby-Phelps & Anza Darehshouri & Lin Xu & Edward A. Fish, 2019. "SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis," Nature, Nature, vol. 569(7757), pages 565-569, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Juan Pang & Fitore Raka & Alya Abbas Heirali & Weijuan Shao & Dinghui Liu & Jianqiu Gu & Jia Nuo Feng & Chieko Mineo & Philip W. Shaul & Xiaoxian Qian & Bryan Coburn & Khosrow Adeli & Wenhua Ling & Ti, 2023. "Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Hend Alhasan & Mohamad Alaa Terkawi & Gen Matsumae & Taku Ebata & Yuan Tian & Tomohiro Shimizu & Yoshio Nishida & Shunichi Yokota & Fayna Garcia-Martin & Mahmoud M. Abd Elwakil & Daisuke Takahashi & M, 2022. "Inhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Liming Yu & Lin Xu & Haiyan Chu & Jun Peng & Anastasia Sacharidou & Hsi-hsien Hsieh & Ada Weinstock & Sohaib Khan & Liqian Ma & José Gabriel Barcia Durán & Jeffrey McDonald & Erik R. Nelson & Sunghee , 2023. "Macrophage-to-endothelial cell crosstalk by the cholesterol metabolite 27HC promotes atherosclerosis in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Anastasia Sacharidou & Ken Chambliss & Jun Peng & Jose Barrera & Keiji Tanigaki & Katherine Luby-Phelps & İpek Özdemir & Sohaib Khan & Shashank R. Sirsi & Sung Hoon Kim & Benita S. Katzenellenbogen & , 2023. "Endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33202-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.