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Tytuł:
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HDAC3 inhibitor suppresses endothelial-to-mesenchymal transition via modulating inflammatory response in atherosclerosis.
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Autorzy:
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Chen L; Department of Medical Laboratory Animal Science, Xi'an Jiaotong University Health Science Center, Xi'an, China; Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China.
Shang C; Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Wang B; Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Wang G; Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Jin Z; Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Yao F; Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Yue Z; Department of Medical Laboratory Animal Science, Xi'an Jiaotong University Health Science Center, Xi'an, China; Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China.
Bai L; Department of Medical Laboratory Animal Science, Xi'an Jiaotong University Health Science Center, Xi'an, China; Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China.
Wang R; Department of Medical Laboratory Animal Science, Xi'an Jiaotong University Health Science Center, Xi'an, China; Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China.
Zhao S; Department of Medical Laboratory Animal Science, Xi'an Jiaotong University Health Science Center, Xi'an, China; Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China.
Liu E; Department of Medical Laboratory Animal Science, Xi'an Jiaotong University Health Science Center, Xi'an, China; Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China.
Wang W; Department of Medical Laboratory Animal Science, Xi'an Jiaotong University Health Science Center, Xi'an, China; Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China. Electronic address: .
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Źródło:
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Biochemical pharmacology [Biochem Pharmacol] 2021 Oct; Vol. 192, pp. 114716. Date of Electronic Publication: 2021 Jul 30.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
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MeSH Terms:
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Atherosclerosis/*metabolism
Endothelium/*metabolism
Epithelial-Mesenchymal Transition/*physiology
Histone Deacetylase Inhibitors/*pharmacology
Histone Deacetylases/*metabolism
Inflammation Mediators/*metabolism
Acrylamides/pharmacology ; Acrylamides/therapeutic use ; Animals ; Atherosclerosis/drug therapy ; Endothelium/drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Histone Deacetylase Inhibitors/therapeutic use ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Inflammation Mediators/antagonists & inhibitors ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenylenediamines/pharmacology ; Phenylenediamines/therapeutic use ; THP-1 Cells
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Contributed Indexing:
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Keywords: Atherosclerosis; Endothelial-to-mesenchymal transition; HDAC3; HUVECs; Inflammation
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Substance Nomenclature:
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0 (Acrylamides)
0 (Histone Deacetylase Inhibitors)
0 (Inflammation Mediators)
0 (Phenylenediamines)
0 (RGFP966)
EC 3.5.1.98 (Histone Deacetylases)
EC 3.5.1.98 (histone deacetylase 3)
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Entry Date(s):
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Date Created: 20210802 Date Completed: 20211116 Latest Revision: 20211116
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Update Code:
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20240105
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DOI:
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10.1016/j.bcp.2021.114716
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PMID:
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34339713
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A total number of 18 different isoforms of histone deacetylases (HDACs) which were categorized into 4 classes have been identified in human. HDAC3 is categorized as class I HDACs and is closely related to the occurrence and development of atherosclerosis. Recent evidence has pointed to endothelial-to-mesenchymal transition (EndMT) as a key process in vascular inflammation in atherosclerosis. However, little is known about the effect of HDAC3 on EndMT in atherosclerosis. Therefore, we aimed to investigate the effect of HDAC3 specific inhibitor on EndMT in ApoE -/- mice fed a Western diet and human umbilical vein endothelial cells (HUVECs) induced by inflammatory cytokines. Firstly, we found that HDAC3 expression was up-regulated and EndMT occurred in the aortas of ApoE -/- mice compared with C57BL/6J mice. However, HDAC3 specific inhibitor RGFP966 alleviated atherosclerotic lesions and inhibited EndMT of the atherosclerotic plaque in ApoE -/- mice. Then, in vitro study showed that inflammatory cytokines TNF-α and IL-1β co-treatment increased the expression of HDAC3 and induced EndMT in HUVECs. HDAC3 inhibition by siRNA or specific inhibitor RGFP966 suppressed EndMT in HUVECs stimulated with TNF-α and IL-1β. By contrast, HDAC3 overexpression by adenovirus further promoted EndMT of HUVECs. In addition, we found that HDAC3 also regulated the inflammatory response of HUVECs by modulating the expression of inflammatory cytokines and the number of monocytes attached to HUVECs. These above results suggest that HDAC3 inhibitor suppresses EndMT via modulating inflammatory response in ApoE -/- mice and HUVECs.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
