Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE-/- mice
Copyright © 2018 Elsevier B.V. All rights reserved..
BACKGROUND: Vasa vasorum (VV) angiogenesis is increased in type 2 diabetes mellitus (T2DM) and may promote atherosclerotic plaque rupture. We sought to determine whether insulin resistance adipocyte-derived exosomes (IRADEs) played a major role in modulating VV angiogenesis and the mechanisms involved.
METHODS: The characterization of IRADEs was performed by electron microscopy, NTA (Nanoparticle Tracking Analysis) and western blot. The cellular effects of IRADEs on angiogenesis were explored in human umbilical vein endothelial cells (HUVECs) and murine aortic endothelial cells (MAECs) in vitro. The roles of IRADEs in angiogenesis were demonstrated with aortic ring and matrigel plug assays ex vivo and the plaque burden, plaque stability and angiogenesis-related protein expression in vivo were evaluated by ultrasonography, immunohistochemistry and western blot.
RESULTS: The IRADEs had a cup-shaped morphology, could be taken up by HUVECs and atherosclerotic plaques, and promoted tube formation by shh in vitro. In the aortic ring and matrigel plug assays, angiogenesis was significantly increased in the IRADEs group. Exogenously administered shh-containing IRADEs increased VV angiogenesis, the plaque burden, the vulnerability index and the expression of angiogenesis-related factors, whereas these effects were attenuated by silencing shh in IRADEs.
CONCLUSIONS: In conclusion, IRADEs promote plaque burden and plaque vulnerability partly by inducing VV angiogenesis, which occurs partly through shh. Accordingly, the application of IRADEs may serve as a novel therapeutic approach to treat diabetic atherosclerosis.
| Errataetall: |
CommentIn: Int J Cardiol. 2021 Nov 15;343:14. - PMID 34537305 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:265 |
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| Enthalten in: |
International journal of cardiology - 265(2018) vom: 15. Aug., Seite 181-187 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Feng [VerfasserIn] |
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| Links: |
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| Themen: |
Adipocyte-derived exosomes |
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| Anmerkungen: |
Date Completed 14.01.2019 Date Revised 18.10.2021 published: Print-Electronic CommentIn: Int J Cardiol. 2021 Nov 15;343:14. - PMID 34537305 Citation Status MEDLINE |
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| doi: |
10.1016/j.ijcard.2018.04.028 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM283335572 |
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| 100 | 1 | |a Wang, Feng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE-/- mice |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Revised 18.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Int J Cardiol. 2021 Nov 15;343:14. - PMID 34537305 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Vasa vasorum (VV) angiogenesis is increased in type 2 diabetes mellitus (T2DM) and may promote atherosclerotic plaque rupture. We sought to determine whether insulin resistance adipocyte-derived exosomes (IRADEs) played a major role in modulating VV angiogenesis and the mechanisms involved | ||
| 520 | |a METHODS: The characterization of IRADEs was performed by electron microscopy, NTA (Nanoparticle Tracking Analysis) and western blot. The cellular effects of IRADEs on angiogenesis were explored in human umbilical vein endothelial cells (HUVECs) and murine aortic endothelial cells (MAECs) in vitro. The roles of IRADEs in angiogenesis were demonstrated with aortic ring and matrigel plug assays ex vivo and the plaque burden, plaque stability and angiogenesis-related protein expression in vivo were evaluated by ultrasonography, immunohistochemistry and western blot | ||
| 520 | |a RESULTS: The IRADEs had a cup-shaped morphology, could be taken up by HUVECs and atherosclerotic plaques, and promoted tube formation by shh in vitro. In the aortic ring and matrigel plug assays, angiogenesis was significantly increased in the IRADEs group. Exogenously administered shh-containing IRADEs increased VV angiogenesis, the plaque burden, the vulnerability index and the expression of angiogenesis-related factors, whereas these effects were attenuated by silencing shh in IRADEs | ||
| 520 | |a CONCLUSIONS: In conclusion, IRADEs promote plaque burden and plaque vulnerability partly by inducing VV angiogenesis, which occurs partly through shh. Accordingly, the application of IRADEs may serve as a novel therapeutic approach to treat diabetic atherosclerosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adipocyte-derived exosomes | |
| 650 | 4 | |a Angiogenesis | |
| 650 | 4 | |a Atherosclerosis | |
| 650 | 4 | |a Sonic hedgehog | |
| 650 | 4 | |a Vasa vasorum | |
| 650 | 7 | |a Apolipoproteins E |2 NLM | |
| 700 | 1 | |a Chen, Fang-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Yuan-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhi-Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yi-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Ti, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Ming |e verfasserin |4 aut | |
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