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

Cited 6 time in scopus
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Title
Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia
Author(s)
S H Lee; N Kim; M Kim; S H Woo; I Han; J Park; K Kim; K S Park; K Kim; D Shim; S E Park; J Y Zhang; D M Go; D Y Kim; Woon Kee Yoon; S P Lee; J Chung; K W Kim; J H Park; S H Lee; S Lee; S J Ann; S H Lee; H S Ahn; S C Jeong; T K Kim; G T Oh; W Y Park; H O Lee; J H Choi
Bibliographic Citation
Nature Communications, vol. 13, pp. 5461-5461
Publication Year
2022
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.
ISSN
2041-1723
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41467-022-33202-2
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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