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Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages.
Sivasubramaniyam, Tharini; Yang, Jiaqi; Cheng, Henry S; Zyla, Alexandra; Li, Angela; Besla, Rickvinder; Dotan, Idit; Revelo, Xavier S; Shi, Sally Yu; Le, Helen; Schroer, Stephanie A; Dodington, David W; Park, Yoo Jin; Kim, Min Jeong; Febbraro, Daniella; Ruel, Isabelle; Genest, Jacques; Kim, Raymond H; Mak, Tak W; Winer, Daniel A; Robbins, Clinton S; Woo, Minna.
Afiliación
  • Sivasubramaniyam T; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Yang J; Institute of Medical Science, University of Toronto, Toronto, ON, M5G 2M9, Canada.
  • Cheng HS; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Zyla A; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Li A; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Besla R; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Dotan I; Department of Immunology, University of Toronto, Toronto, ON, M5G 2M9, Canada.
  • Revelo XS; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Shi SY; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5G 2M9, Canada.
  • Le H; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Schroer SA; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Dodington DW; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Park YJ; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Kim MJ; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Febbraro D; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Ruel I; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Genest J; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Kim RH; Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 03181, Korea.
  • Mak TW; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.
  • Winer DA; Institute of Medical Science, University of Toronto, Toronto, ON, M5G 2M9, Canada.
  • Robbins CS; Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, QC, H4A 3J1, Canada.
  • Woo M; Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, QC, H4A 3J1, Canada.
Sci Rep ; 11(1): 4723, 2021 02 25.
Article en En | MEDLINE | ID: mdl-33633277
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Proteína Desglicasa DJ-1 / Inflamación Límite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Proteína Desglicasa DJ-1 / Inflamación Límite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido