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

التفاصيل البيبلوغرافية
العنوان: Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia.
المؤلفون: Lee SH; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Kim N; Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.; Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Republic of Korea., Kim M; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Woo SH; Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Han I; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Park J; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Kim K; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Park KS; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Kim K; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Shim D; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Park SE; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Zhang JY; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Go DM; Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Kim DY; Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Yoon WK; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, 28116, Republic of Korea., Lee SP; Cardiovascular Center and Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea., Chung J; Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea., Kim KW; Department of Pharmacology and Regenerative Medicine, The University of Illinois College of Medicine, Chicago, IL, 60612, USA., Park JH; Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, 04763, Republic of Korea., Lee SH; Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea., Lee S; Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea., Ann SJ; Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea., Lee SH; Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea., Ahn HS; Division of Cardiology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, 11765, Republic of Korea.; Catholic Research Institute for Intractable Cardiovascular Disease (CRID), College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea., Jeong SC; Department of Thoracic and Cardiovascular Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, 11765, Republic of Korea., Kim TK; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Oh GT; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Park WY; Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea.; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences &Technology, Sungkyunkwan University, Seoul, 06355, Republic of Korea., Lee HO; Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. haeocklee@catholic.ac.kr.; Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Republic of Korea. haeocklee@catholic.ac.kr., Choi JH; Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea. jchoi75@hanyang.ac.kr.
المصدر: Nature communications [Nat Commun] 2022 Sep 17; Vol. 13 (1), pp. 5461. Date of Electronic Publication: 2022 Sep 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Aortic Valve Stenosis* , Calcinosis*/genetics , Hyperlipidemias*/genetics , Hyperlipidemias*/metabolism, Animals ; Aortic Valve/metabolism ; Cells, Cultured ; Endothelial Cells/metabolism ; Humans ; Immunomodulation ; Inflammation/genetics ; Inflammation/metabolism ; Lipoproteins, LDL/metabolism ; Mice ; PPAR gamma/genetics ; PPAR gamma/metabolism ; Pioglitazone/pharmacology ; Transcriptome
مستخلص: 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-II hi 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).)
References: J Lipid Res. 2008 Oct;49(10):2230-9. (PMID: 18594118)
Nat Methods. 2017 Nov;14(11):1083-1086. (PMID: 28991892)
Circulation. 2019 Jul 9;140(2):147-163. (PMID: 31146585)
J Lipid Res. 1998 Apr;39(4):777-88. (PMID: 9555943)
J Biol Chem. 1998 Nov 13;273(46):30427-34. (PMID: 9804809)
Circ Res. 2008 Feb 15;102(3):283-94. (PMID: 18276926)
Cardiovasc Drugs Ther. 2016 Feb;30(1):87-100. (PMID: 26896185)
Atherosclerosis. 2014 Aug;235(2):398-407. (PMID: 24929820)
Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):523-32. (PMID: 23288158)
Int J Inflam. 2011;2011:364310. (PMID: 21826258)
N Engl J Med. 2005 Jun 9;352(23):2389-97. (PMID: 15944423)
J Am Coll Cardiol. 2014 Feb 11;63(5):470-7. (PMID: 24161338)
Cell Rep. 2019 May 28;27(9):2748-2758.e3. (PMID: 31141696)
N Engl J Med. 2010 Oct 21;363(17):1597-607. (PMID: 20961243)
Cancer Discov. 2019 Dec;9(12):1720-1735. (PMID: 31578185)
Cell. 2020 Feb 20;180(4):764-779.e20. (PMID: 32059779)
J Am Coll Cardiol. 2019 May 7;73(17):2150-2162. (PMID: 31047003)
N Engl J Med. 2013 Feb 7;368(6):503-12. (PMID: 23388002)
Nature. 2005 Sep 29;437(7059):759-63. (PMID: 16127449)
J Am Coll Cardiol. 2015 Sep 15;66(11):1236-1246. (PMID: 26361154)
Atherosclerosis. 2016 Aug;251:109-118. (PMID: 27318830)
Cell Rep. 2020 Feb 11;30(6):1923-1934.e4. (PMID: 32049021)
Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2910-2921. (PMID: 33086873)
Arterioscler Thromb Vasc Biol. 2020 Jun;40(6):e153-e165. (PMID: 32295422)
Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):230-9. (PMID: 14592855)
J Am Coll Cardiol. 2007 Jan 23;49(3):290-7. (PMID: 17239709)
Circulation. 2007 Jan 23;115(3):377-86. (PMID: 17224478)
Circ Res. 2014 May 23;114(11):1684-9. (PMID: 24677271)
J Biol Chem. 1997 May 16;272(20):12938-44. (PMID: 9148899)
Immunity. 2018 Dec 18;49(6):1191. (PMID: 30566884)
J Biol Chem. 2002 May 31;277(22):19649-57. (PMID: 11877444)
Dev Cell. 2019 Mar 11;48(5):617-630.e3. (PMID: 30799229)
Nat Methods. 2017 Oct;14(10):979-982. (PMID: 28825705)
Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):225-31. (PMID: 19926833)
N Engl J Med. 2014 Aug 21;371(8):744-56. (PMID: 25140960)
Trends Endocrinol Metab. 2014 Feb;25(2):99-106. (PMID: 24315207)
J Am Coll Cardiol. 2012 Nov 6;60(19):1854-63. (PMID: 23062541)
Nat Rev Cardiol. 2014 Apr;11(4):218-31. (PMID: 24445487)
Genet Med. 2018 Jun;20(6):591-598. (PMID: 29261184)
J Mol Cell Cardiol. 2009 Dec;47(6):828-34. (PMID: 19695258)
Circulation. 2020 May 26;141(21):1670-1680. (PMID: 32223336)
J Vis Exp. 2010 Dec 29;(46):. (PMID: 21248687)
Korean Circ J. 2018 Jul;48(7):591-601. (PMID: 29968431)
Circulation. 2015 Aug 25;132(8):677-90. (PMID: 26224810)
Nat Struct Mol Biol. 2008 Sep;15(9):924-31. (PMID: 19172745)
Eur J Cardiothorac Surg. 2006 Nov;30(5):722-7. (PMID: 16950629)
J Lipid Res. 2002 Feb;43(2):177-86. (PMID: 11861659)
Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1580-8. (PMID: 21493891)
Nat Commun. 2012;3:1300. (PMID: 23250430)
J Clin Endocrinol Metab. 2016 Sep;101(9):3281-7. (PMID: 27218270)
JACC Basic Transl Sci. 2020 Jul 01;5(7):649-661. (PMID: 32760854)
Cell. 2019 Jun 13;177(7):1888-1902.e21. (PMID: 31178118)
Nature. 2019 May;569(7757):565-569. (PMID: 31019307)
Circulation. 2010 Jan 19;121(2):306-14. (PMID: 20048204)
Arterioscler Thromb Vasc Biol. 2020 Nov;40(11):e296-e308. (PMID: 32938214)
Circulation. 2020 Jan 14;141(2):132-146. (PMID: 31928435)
Development. 2019 Mar 12;146(12):. (PMID: 30796046)
J Am Coll Cardiol. 2015 Dec 22;66(24):2687-2695. (PMID: 26700830)
Blood. 2011 Jan 6;117(1):88-97. (PMID: 20930067)
J Exp Med. 2006 May 15;203(5):1221-33. (PMID: 16618794)
Science. 2019 Mar 15;363(6432):. (PMID: 30872492)
Nat Med. 2013 May;19(5):557-66. (PMID: 23652116)
Can J Cardiol. 2014 Sep;30(9):962-70. (PMID: 24986049)
N Engl J Med. 2008 Sep 25;359(13):1343-56. (PMID: 18765433)
Mol Cell. 2001 Jan;7(1):161-71. (PMID: 11172721)
PPAR Res. 2016;2016:6042162. (PMID: 27148361)
Eur Heart J. 2020 Oct 21;41(40):3913-3920. (PMID: 32076698)
Arthritis Rheum. 2002 Mar;46(3):824-36. (PMID: 11920421)
J Lipid Res. 2004 Dec;45(12):2161-73. (PMID: 15489539)
J Exp Med. 2009 Mar 16;206(3):497-505. (PMID: 19221394)
Circ Res. 2018 Oct 26;123(10):1127-1142. (PMID: 30359200)
معلومات مُعتمدة: R01 DK126753 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (Lipoproteins, LDL)
0 (PPAR gamma)
X4OV71U42S (Pioglitazone)
تواريخ الأحداث: Date Created: 20220917 Date Completed: 20220920 Latest Revision: 20221102
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9482653
DOI: 10.1038/s41467-022-33202-2
PMID: 36115863
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-022-33202-2