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

DC Field Value Language
dc.contributor.author안수진-
dc.contributor.author이삭-
dc.contributor.author이상학-
dc.contributor.author이승현-
dc.date.accessioned2023-03-10T01:35:40Z-
dc.date.available2023-03-10T01:35:40Z-
dc.date.issued2022-09-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/193251-
dc.description.abstractValvular 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.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHAortic Valve / metabolism-
dc.subject.MESHAortic Valve Stenosis*-
dc.subject.MESHCalcinosis* / genetics-
dc.subject.MESHCells, Cultured-
dc.subject.MESHEndothelial Cells / metabolism-
dc.subject.MESHHumans-
dc.subject.MESHHyperlipidemias* / genetics-
dc.subject.MESHHyperlipidemias* / metabolism-
dc.subject.MESHImmunomodulation-
dc.subject.MESHInflammation / genetics-
dc.subject.MESHInflammation / metabolism-
dc.subject.MESHLipoproteins, LDL / metabolism-
dc.subject.MESHMice-
dc.subject.MESHPPAR gamma / genetics-
dc.subject.MESHPPAR gamma / metabolism-
dc.subject.MESHPioglitazone / pharmacology-
dc.subject.MESHTranscriptome-
dc.titleSingle-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorSeung Hyun Lee-
dc.contributor.googleauthorNayoung Kim-
dc.contributor.googleauthorMinkyu Kim-
dc.contributor.googleauthorSang-Ho Woo-
dc.contributor.googleauthorInhee Han-
dc.contributor.googleauthorJisu Park-
dc.contributor.googleauthorKyeongdae Kim-
dc.contributor.googleauthorKyu Seong Park-
dc.contributor.googleauthorKibyeong Kim-
dc.contributor.googleauthorDahee Shim-
dc.contributor.googleauthorSang-Eun Park-
dc.contributor.googleauthorJing Yu Zhang-
dc.contributor.googleauthorDu-Min Go-
dc.contributor.googleauthorDae-Yong Kim-
dc.contributor.googleauthorWon Kee Yoon-
dc.contributor.googleauthorSeung-Pyo Lee-
dc.contributor.googleauthorJongsuk Chung-
dc.contributor.googleauthorKi-Wook Kim-
dc.contributor.googleauthorJung Hwan Park-
dc.contributor.googleauthorSeung Hyun Lee-
dc.contributor.googleauthorSak Lee-
dc.contributor.googleauthorSoo-Jin Ann-
dc.contributor.googleauthorSang-Hak Lee-
dc.contributor.googleauthorHyo-Suk Ahn-
dc.contributor.googleauthorSeong Cheol Jeong-
dc.contributor.googleauthorTae Kyeong Kim-
dc.contributor.googleauthorGoo Taeg Oh-
dc.contributor.googleauthorWoong-Yang Park-
dc.contributor.googleauthorHae-Ock Lee-
dc.contributor.googleauthorJae-Hoon Choi-
dc.identifier.doi10.1038/s41467-022-33202-2-
dc.contributor.localIdA02243-
dc.contributor.localIdA02807-
dc.contributor.localIdA02833-
dc.contributor.localIdA02935-
dc.relation.journalcodeJ02293-
dc.identifier.eissn2041-1723-
dc.identifier.pmid36115863-
dc.contributor.alternativeNameAnn, Soo Jin-
dc.contributor.affiliatedAuthor안수진-
dc.contributor.affiliatedAuthor이삭-
dc.contributor.affiliatedAuthor이상학-
dc.contributor.affiliatedAuthor이승현-
dc.citation.volume13-
dc.citation.number1-
dc.citation.startPage5461-
dc.identifier.bibliographicCitationNATURE COMMUNICATIONS, Vol.13(1) : 5461, 2022-09-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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