Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages
Abstract Inflammation is a key contributor to atherosclerosis with macrophages playing a pivotal role through the induction of oxidative stress and cytokine/chemokine secretion. DJ1, an anti-oxidant protein, has shown to paradoxically protect against chronic and acute inflammation. However, the role...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84063-6 |
| _version_ | 1818996314086572032 |
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| author | Tharini Sivasubramaniyam Jiaqi Yang Henry S. Cheng Alexandra Zyla Angela Li Rickvinder Besla Idit Dotan Xavier S. Revelo Sally Yu Shi Helen Le Stephanie A. Schroer David W. Dodington Yoo Jin Park Min Jeong Kim Daniella Febbraro Isabelle Ruel Jacques Genest Raymond H. Kim Tak W. Mak Daniel A. Winer Clinton S. Robbins Minna Woo |
| author_facet | Tharini Sivasubramaniyam Jiaqi Yang Henry S. Cheng Alexandra Zyla Angela Li Rickvinder Besla Idit Dotan Xavier S. Revelo Sally Yu Shi Helen Le Stephanie A. Schroer David W. Dodington Yoo Jin Park Min Jeong Kim Daniella Febbraro Isabelle Ruel Jacques Genest Raymond H. Kim Tak W. Mak Daniel A. Winer Clinton S. Robbins Minna Woo |
| author_sort | Tharini Sivasubramaniyam |
| collection | DOAJ |
| description | Abstract Inflammation is a key contributor to atherosclerosis with macrophages playing a pivotal role through the induction of oxidative stress and cytokine/chemokine secretion. DJ1, an anti-oxidant protein, has shown to paradoxically protect against chronic and acute inflammation. However, the role of DJ1 in atherosclerosis remains elusive. To assess the role of Dj1 in atherogenesis, we generated whole-body Dj1-deficient atherosclerosis-prone Apoe null mice (Dj1 −/− Apoe −/− ). After 21 weeks of atherogenic diet, Dj1 −/− Apoe −/− mice were protected against atherosclerosis with significantly reduced plaque macrophage content. To assess whether haematopoietic or parenchymal Dj1 contributed to atheroprotection in Dj1-deficient mice, we performed bone-marrow (BM) transplantation and show that Dj1-deficient BM contributed to their attenuation in atherosclerosis. To assess cell-autonomous role of macrophage Dj1 in atheroprotection, BM-derived macrophages from Dj1-deficient mice and Dj1-silenced macrophages were assessed in response to oxidized low-density lipoprotein (oxLDL). In both cases, there was an enhanced anti-inflammatory response which may have contributed to atheroprotection in Dj1-deficient mice. There was also an increased trend of plasma DJ-1 levels from individuals with ischemic heart disease compared to those without. Our findings indicate an atheropromoting role of Dj1 and suggests that targeting Dj1 may provide a novel therapeutic avenue for atherosclerosis treatment or prevention. |
| first_indexed | 2024-12-20T21:27:46Z |
| format | Article |
| id | doaj.art-dd1b0c94e3934c83829b8e94c00d30fc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:27:46Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dd1b0c94e3934c83829b8e94c00d30fc2022-12-21T19:26:07ZengNature PortfolioScientific Reports2045-23222021-02-0111111210.1038/s41598-021-84063-6Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophagesTharini Sivasubramaniyam0Jiaqi Yang1Henry S. Cheng2Alexandra Zyla3Angela Li4Rickvinder Besla5Idit Dotan6Xavier S. Revelo7Sally Yu Shi8Helen Le9Stephanie A. Schroer10David W. Dodington11Yoo Jin Park12Min Jeong Kim13Daniella Febbraro14Isabelle Ruel15Jacques Genest16Raymond H. Kim17Tak W. Mak18Daniel A. Winer19Clinton S. Robbins20Minna Woo21Toronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkResearch Institute of the McGill University Health Centre, Royal Victoria HospitalResearch Institute of the McGill University Health Centre, Royal Victoria HospitalDepartment of Medicine, University Health Network/Sinai Health System, University of TorontoDepartment of Immunology, University of TorontoToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkToronto General Hospital Research Institute, University Health NetworkAbstract Inflammation is a key contributor to atherosclerosis with macrophages playing a pivotal role through the induction of oxidative stress and cytokine/chemokine secretion. DJ1, an anti-oxidant protein, has shown to paradoxically protect against chronic and acute inflammation. However, the role of DJ1 in atherosclerosis remains elusive. To assess the role of Dj1 in atherogenesis, we generated whole-body Dj1-deficient atherosclerosis-prone Apoe null mice (Dj1 −/− Apoe −/− ). After 21 weeks of atherogenic diet, Dj1 −/− Apoe −/− mice were protected against atherosclerosis with significantly reduced plaque macrophage content. To assess whether haematopoietic or parenchymal Dj1 contributed to atheroprotection in Dj1-deficient mice, we performed bone-marrow (BM) transplantation and show that Dj1-deficient BM contributed to their attenuation in atherosclerosis. To assess cell-autonomous role of macrophage Dj1 in atheroprotection, BM-derived macrophages from Dj1-deficient mice and Dj1-silenced macrophages were assessed in response to oxidized low-density lipoprotein (oxLDL). In both cases, there was an enhanced anti-inflammatory response which may have contributed to atheroprotection in Dj1-deficient mice. There was also an increased trend of plasma DJ-1 levels from individuals with ischemic heart disease compared to those without. Our findings indicate an atheropromoting role of Dj1 and suggests that targeting Dj1 may provide a novel therapeutic avenue for atherosclerosis treatment or prevention.https://doi.org/10.1038/s41598-021-84063-6 |
| spellingShingle | Tharini Sivasubramaniyam Jiaqi Yang Henry S. Cheng Alexandra Zyla Angela Li Rickvinder Besla Idit Dotan Xavier S. Revelo Sally Yu Shi Helen Le Stephanie A. Schroer David W. Dodington Yoo Jin Park Min Jeong Kim Daniella Febbraro Isabelle Ruel Jacques Genest Raymond H. Kim Tak W. Mak Daniel A. Winer Clinton S. Robbins Minna Woo Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages Scientific Reports |
| title | Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages |
| title_full | Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages |
| title_fullStr | Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages |
| title_full_unstemmed | Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages |
| title_short | Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages |
| title_sort | dj1 deficiency protects against atherosclerosis with anti inflammatory response in macrophages |
| url | https://doi.org/10.1038/s41598-021-84063-6 |
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