@article{be895aaad6234d69a90a02d3a9b5479d,
title = "Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia",
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.",
author = "Lee, {Seung Hyun} and Nayoung Kim and Minkyu Kim and Woo, {Sang Ho} and Inhee Han and Jisu Park and Kyeongdae Kim and Park, {Kyu Seong} and Kibyeong Kim and Dahee Shim and Park, {Sang eun} and Zhang, {Jing Yu} and Go, {Du Min} and Kim, {Dae Yong} and Yoon, {Won Kee} and Lee, {Seung Pyo} and Jongsuk Chung and Kim, {Ki Wook} and Park, {Jung Hwan} and Lee, {Seung Hyun} and Sak Lee and Ann, {Soo jin} and Lee, {Sang Hak} and Ahn, {Hyo Suk} and Jeong, {Seong Cheol} and Kim, {Tae Kyeong} and Oh, {Goo Taeg} and Park, {Woong Yang} and Lee, {Hae Ock} and Choi, {Jae Hoon}",
note = "Funding Information: We acknowledge Taek Chang Lee from Korea Research Institute of Bioscience and Biotechnology (KRIBB) and Sookyoung Kim from Samsung Genome Institute, for their technical supports. We acknowledge Jia Park from D-Lab of Hanyang Institute of Technology for designing the graphical summary of the proposed pathogenesis model. We also acknowledge the KREONET/GLORIAD service provided by the Korea Institute of Science and Technology Information. This work was supported by the National Research Foundation of the Korea grant (NRF 2016M3A9D5A01952413; J.-H.C., 2021R1A2C3004586; J.-H.C., and 2016R1A5A1011974; H.-O.L.) and the National Institutes of Health (R01 DK126753; K.-W.K.). Funding Information: We acknowledge Taek Chang Lee from Korea Research Institute of Bioscience and Biotechnology (KRIBB) and Sookyoung Kim from Samsung Genome Institute, for their technical supports. We acknowledge Jia Park from D-Lab of Hanyang Institute of Technology for designing the graphical summary of the proposed pathogenesis model. We also acknowledge the KREONET/GLORIAD service provided by the Korea Institute of Science and Technology Information. This work was supported by the National Research Foundation of the Korea grant (NRF 2016M3A9D5A01952413; J.-H.C., 2021R1A2C3004586; J.-H.C., and 2016R1A5A1011974; H.-O.L.) and the National Institutes of Health (R01 DK126753; K.-W.K.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-33202-2",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}