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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd1b0c94e3934c83829b8e94c00d30fc
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spelling	oai:doaj.org-article:dd1b0c94e3934c83829b8e94c00d30fc2021-12-02T15:53:46ZDj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages10.1038/s41598-021-84063-62045-2322https://doaj.org/article/dd1b0c94e3934c83829b8e94c00d30fc2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84063-6https://doaj.org/toc/2045-2322Abstract 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.Tharini SivasubramaniyamJiaqi YangHenry S. ChengAlexandra ZylaAngela LiRickvinder BeslaIdit DotanXavier S. ReveloSally Yu ShiHelen LeStephanie A. SchroerDavid W. DodingtonYoo Jin ParkMin Jeong KimDaniella FebbraroIsabelle RuelJacques GenestRaymond H. KimTak W. MakDaniel A. WinerClinton S. RobbinsMinna WooNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dd1b0c94e3934c83829b8e94c00d30fc
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Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages

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