View : 431 Download: 79
Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia
- Title
- Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia
- Authors
- Lee S.H.; Kim N.; Kim M.; Woo S.-H.; Han I.; Park J.; Kim K.; Park K.S.; Shim D.; Park S.-E.; Zhang J.Y.; Go D.-M.; Kim D.-Y.; Yoon W.K.; Lee S.-P.; Chung J.; Kim K.-W.; Park J.H.; Lee S.; Ann S.-J.; Lee S.-H.; Ahn H.-S.; Jeong S.C.; Kim T.K.; Oh G.T.; Park W.-Y.; Lee H.-O.; Choi J.-H.
- Ewha Authors
- 오구택
- SCOPUS Author ID
- 오구택
- Issue Date
- 2022
- Journal Title
- Nature Communications
- ISSN
- 2041-1723
- Citation
- Nature Communications vol. 13, no. 1
- Publisher
- Nature Research
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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. © 2022, The Author(s).
- DOI
- 10.1038/s41467-022-33202-2
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
-
s41467-022-33202-2.pdf(7.41 MB)
Download
- Export
- RIS (EndNote)
- XLS (Excel)
- XML