The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression
Background: Atherosclerosis is a chronic inflammatory vascular disease and the main cause of death and morbidity. Emerging evidence suggests that ubiquitination plays an important role in the pathogenesis of atherosclerosis including control of vascular inflammation, vascular smooth muscle cell (VSM...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/13/2014 |
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| author | Fabienne Burger Daniela Baptista Aline Roth Karim J. Brandt Kapka Miteva |
| author_facet | Fabienne Burger Daniela Baptista Aline Roth Karim J. Brandt Kapka Miteva |
| author_sort | Fabienne Burger |
| collection | DOAJ |
| description | Background: Atherosclerosis is a chronic inflammatory vascular disease and the main cause of death and morbidity. Emerging evidence suggests that ubiquitination plays an important role in the pathogenesis of atherosclerosis including control of vascular inflammation, vascular smooth muscle cell (VSMC) function and atherosclerotic plaque stability. Peli1 a type of E3 ubiquitin ligase has emerged as a critical regulator of innate and adaptive immunity, however, its role in atherosclerosis remains to be elucidated. Methods: Apoe<sup>−/−</sup> mice and Peli1-deficient Apoe<sup>−/−</sup> Peli1<sup>−/−</sup> mice were subject to high cholesterol diet. Post sacrifice, serum was collected, and atherosclerotic plaque size and parameters of atherosclerotic plaque stability were evaluated. Immunoprofiling and foam cell quantification were performed. Results: Peli1 deficiency does not affect atherosclerosis lesion burden and cholesterol levels, but promotes VSMCs foam cells formation, necrotic core expansion, collagen, and fibrous cap reduction. Apoe<sup>−/−</sup> Peli1<sup>−/−</sup> mice exhibit a storm of inflammatory cytokines, expansion of Th1, Th1, Th17, and Tfh cells, a decrease in regulatory T and B cells and induction of pro-atherogenic serum level of IgG2a and IgE. Conclusions: In the present study, we uncover a crucial role for Peli1 in atherosclerosis as an important regulator of inflammation and VSMCs phenotypic modulation and subsequently atherosclerotic plaque destabilization. |
| first_indexed | 2024-03-09T22:01:18Z |
| format | Article |
| id | doaj.art-256086da431b4ceab24d29014d8558cd |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T22:01:18Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-256086da431b4ceab24d29014d8558cd2023-11-23T19:48:03ZengMDPI AGCells2073-44092022-06-011113201410.3390/cells11132014The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis ProgressionFabienne Burger0Daniela Baptista1Aline Roth2Karim J. Brandt3Kapka Miteva4Division of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, CH-1211 Geneva, SwitzerlandDivision of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, CH-1211 Geneva, SwitzerlandDivision of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, CH-1211 Geneva, SwitzerlandDivision of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, CH-1211 Geneva, SwitzerlandDivision of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, CH-1211 Geneva, SwitzerlandBackground: Atherosclerosis is a chronic inflammatory vascular disease and the main cause of death and morbidity. Emerging evidence suggests that ubiquitination plays an important role in the pathogenesis of atherosclerosis including control of vascular inflammation, vascular smooth muscle cell (VSMC) function and atherosclerotic plaque stability. Peli1 a type of E3 ubiquitin ligase has emerged as a critical regulator of innate and adaptive immunity, however, its role in atherosclerosis remains to be elucidated. Methods: Apoe<sup>−/−</sup> mice and Peli1-deficient Apoe<sup>−/−</sup> Peli1<sup>−/−</sup> mice were subject to high cholesterol diet. Post sacrifice, serum was collected, and atherosclerotic plaque size and parameters of atherosclerotic plaque stability were evaluated. Immunoprofiling and foam cell quantification were performed. Results: Peli1 deficiency does not affect atherosclerosis lesion burden and cholesterol levels, but promotes VSMCs foam cells formation, necrotic core expansion, collagen, and fibrous cap reduction. Apoe<sup>−/−</sup> Peli1<sup>−/−</sup> mice exhibit a storm of inflammatory cytokines, expansion of Th1, Th1, Th17, and Tfh cells, a decrease in regulatory T and B cells and induction of pro-atherogenic serum level of IgG2a and IgE. Conclusions: In the present study, we uncover a crucial role for Peli1 in atherosclerosis as an important regulator of inflammation and VSMCs phenotypic modulation and subsequently atherosclerotic plaque destabilization.https://www.mdpi.com/2073-4409/11/13/2014atherosclerosisfoam cellsVSMCsplaque stabilityubiquitin ligase |
| spellingShingle | Fabienne Burger Daniela Baptista Aline Roth Karim J. Brandt Kapka Miteva The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression Cells atherosclerosis foam cells VSMCs plaque stability ubiquitin ligase |
| title | The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression |
| title_full | The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression |
| title_fullStr | The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression |
| title_full_unstemmed | The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression |
| title_short | The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression |
| title_sort | e3 ubiquitin ligase peli1 deficiency promotes atherosclerosis progression |
| topic | atherosclerosis foam cells VSMCs plaque stability ubiquitin ligase |
| url | https://www.mdpi.com/2073-4409/11/13/2014 |
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