Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages
| Autor: | Yoo Jin Park, Minna Woo, David W. Dodington, Helen Le, Angela Li, Stephanie A. Schroer, Xavier S. Revelo, Alexandra Zyla, Jacques Genest, Min Jeong Kim, Daniella Febbraro, Tak W. Mak, Rickvinder Besla, Isabelle Ruel, Daniel A. Winer, Idit Dotan, Henry S. Cheng, Raymond H. Kim, Clinton S. Robbins, Jiaqi Yang, Tharini Sivasubramaniyam, Sally Yu Shi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Mouse Science medicine.medical_treatment Protein Deglycase DJ-1 Inflammation 030204 cardiovascular system & hematology medicine.disease_cause Article 03 medical and health sciences Mice 0302 clinical medicine Animal disease models Medicine Macrophage Animals Humans Cells Cultured Mice Knockout Multidisciplinary business.industry Macrophages Middle Aged Protective Factors Atherosclerosis Transplantation 030104 developmental biology Cytokine Mechanisms of disease RAW 264.7 Cells Chemokine secretion Immunology Female medicine.symptom business Oxidative stress Gene Deletion Lipoprotein |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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