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

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 LeeSak 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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish
Article number5461
JournalNature Communications
Issue number1
StatePublished - Dec 2022

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© 2022, The Author(s).


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