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

Authors
 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  ;  Won Kee Yoon  ;  Seung-Pyo Lee  ;  Jongsuk Chung  ;  Ki-Wook Kim  ;  Jung Hwan Park  ;  Seung Hyun Lee  ;  Sak Lee  ;  Soo-Jin Ann  ;  Sang-Hak Lee  ;  Hyo-Suk Ahn  ;  Seong Cheol Jeong  ;  Tae Kyeong Kim  ;  Goo Taeg Oh  ;  Woong-Yang Park  ;  Hae-Ock Lee  ;  Jae-Hoon Choi 
Citation
 NATURE COMMUNICATIONS, Vol.13(1) : 5461, 2022-09 
Journal Title
NATURE COMMUNICATIONS
Issue Date
2022-09
MeSH
Animals ; Aortic Valve / metabolism ; Aortic Valve Stenosis* ; Calcinosis* / genetics ; Cells, Cultured ; Endothelial Cells / metabolism ; Humans ; Hyperlipidemias* / genetics ; Hyperlipidemias* / metabolism ; Immunomodulation ; Inflammation / genetics ; Inflammation / metabolism ; Lipoproteins, LDL / metabolism ; Mice ; PPAR gamma / genetics ; PPAR gamma / metabolism ; Pioglitazone / pharmacology ; Transcriptome
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.
DOI
10.1038/s41467-022-33202-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Ann, Soo Jin(안수진)
Lee, Sak(이삭) ORCID logo https://orcid.org/0000-0001-6130-2342
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Lee, Seung Hyun(이승현) ORCID logo https://orcid.org/0000-0002-0311-6565
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193251
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