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- Title
Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia.
- Authors
Lee, Seung Hyun; Kim, Nayoung; Kim, Minkyu; Woo, Sang-Ho; Han, Inhee; Park, Jisu; Kim, Kyeongdae; Park, Kyu Seong; Kim, Kibyeong; Shim, Dahee; Park, Sang-eun; Zhang, Jing Yu; Go, Du-Min; Kim, Dae-Yong; Yoon, Won Kee; Lee, Seung-Pyo; Chung, Jongsuk; Kim, Ki-Wook; Park, Jung Hwan; Lee, Sak
- 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. Identifying the mechanisms underlying the early inflammatory phase of aortic valve disease is crucial for disease prevention. Here the authors perform single-cell RNA sequencing to show the immunomodulatory role of PPARγ in valvular endothelial cells during hyperlipidemia.
- Subjects
AORTIC valve; AORTIC valve diseases; HYPERLIPIDEMIA; RNA sequencing; BLOOD lipids; MONOCYTES
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-33202-2