ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development
To determine the roles of endoplasmic reticulum (ER) stress and trained immunity, we performed transcriptome analyses on the thoracic aorta (TA) and abdominal aorta (AA) from the angiotensin II (Ang II)-HFD-ApoE-KO aneurysm model and made significant findings: 1) Ang II bypassed HFD-induced metaboli...
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Frontiers Media S.A.
2023-09-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1268916/full |
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author | Yifan Lu Yu Sun Fatma Saaoud Ying Shao Keman Xu Xiaohua Jiang Xiaohua Jiang Sheng Wu Jun Yu Nathaniel W. Snyder Ling Yang Xinghua Mindy Shi Huaqing Zhao Hong Wang Xiaofeng Yang Xiaofeng Yang |
author_facet | Yifan Lu Yu Sun Fatma Saaoud Ying Shao Keman Xu Xiaohua Jiang Xiaohua Jiang Sheng Wu Jun Yu Nathaniel W. Snyder Ling Yang Xinghua Mindy Shi Huaqing Zhao Hong Wang Xiaofeng Yang Xiaofeng Yang |
author_sort | Yifan Lu |
collection | DOAJ |
description | To determine the roles of endoplasmic reticulum (ER) stress and trained immunity, we performed transcriptome analyses on the thoracic aorta (TA) and abdominal aorta (AA) from the angiotensin II (Ang II)-HFD-ApoE-KO aneurysm model and made significant findings: 1) Ang II bypassed HFD-induced metabolic reprogramming and induced stronger inflammation in AA than in TA; 2) Ang II and HFD upregulated 890 genes in AA versus TA and induced cytokine signaling; 3) Ang II AA and TA upregulated 73 and 68 cytokines, scRNA-Seq identified markers of macrophages and immune cells, cell death regulators, respectively; transdifferentiation markers of neuron, glial, and squamous epithelial cells were upregulated by Ang II-AA and TA; and pyroptosis signaling with IL-1β and caspase-4 were more upregulated in Ang II-AA than in TA; 4) Six upregulated transcriptomes in patients with AAA, Ang II AA, Ang II TA, additional aneurysm models, PPE-AAA and BAPN-Ang II-AAA, were partially overlapped with 10 lists of new ER stress gene sets including 3 interaction protein lists of ER stress regulators ATF6, PERK, and IRE1, HPA ER localization genes, KEGG signal genes, XBP1 transcription targets, ATF4 (PERK) targets, ATF6 targets, thapsigargin ER stress genes, tunicamycin-ER stress genes, respectively; 5) Ang II-AA and TA upregulated ROS regulators, MitoCarta genes, trained immunity genes, and glycolysis genes; and 6) Gene KO transcriptomes indicated that ATF6 and PERK played more significant roles than IRE1 in promoting AAA and trained immunity whereas antioxidant NRF2 inhibited them. Our unprecedented ER-focused transcriptomic analyses have provided novel insights on the roles of ER as an immune organelle in sensing various DAMPs and initiating ER stress that triggers Ang II-accelerated trained immunity and differs susceptibilities of thoracic and abdominal aortas to diseases. |
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institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-03-12T02:39:39Z |
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spelling | doaj.art-c85967b978be4ba9a3dd6e4e1dd1d7572023-09-04T08:35:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12689161268916ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm developmentYifan Lu0Yu Sun1Fatma Saaoud2Ying Shao3Keman Xu4Xiaohua Jiang5Xiaohua Jiang6Sheng Wu7Jun Yu8Nathaniel W. Snyder9Ling Yang10Xinghua Mindy Shi11Huaqing Zhao12Hong Wang13Xiaofeng Yang14Xiaofeng Yang15Centers of Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters of Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters of Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters of Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters of Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters of Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research and Thrombosis Research Center, Departments of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research and Thrombosis Research Center, Departments of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research and Thrombosis Research Center, Departments of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research and Thrombosis Research Center, Departments of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMedical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesDepartment of Computer and Information Sciences, College of Science and Technology, Temple University, Philadelphia, PA, United StatesBiomedical Education and Data Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research and Thrombosis Research Center, Departments of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters of Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research and Thrombosis Research Center, Departments of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesTo determine the roles of endoplasmic reticulum (ER) stress and trained immunity, we performed transcriptome analyses on the thoracic aorta (TA) and abdominal aorta (AA) from the angiotensin II (Ang II)-HFD-ApoE-KO aneurysm model and made significant findings: 1) Ang II bypassed HFD-induced metabolic reprogramming and induced stronger inflammation in AA than in TA; 2) Ang II and HFD upregulated 890 genes in AA versus TA and induced cytokine signaling; 3) Ang II AA and TA upregulated 73 and 68 cytokines, scRNA-Seq identified markers of macrophages and immune cells, cell death regulators, respectively; transdifferentiation markers of neuron, glial, and squamous epithelial cells were upregulated by Ang II-AA and TA; and pyroptosis signaling with IL-1β and caspase-4 were more upregulated in Ang II-AA than in TA; 4) Six upregulated transcriptomes in patients with AAA, Ang II AA, Ang II TA, additional aneurysm models, PPE-AAA and BAPN-Ang II-AAA, were partially overlapped with 10 lists of new ER stress gene sets including 3 interaction protein lists of ER stress regulators ATF6, PERK, and IRE1, HPA ER localization genes, KEGG signal genes, XBP1 transcription targets, ATF4 (PERK) targets, ATF6 targets, thapsigargin ER stress genes, tunicamycin-ER stress genes, respectively; 5) Ang II-AA and TA upregulated ROS regulators, MitoCarta genes, trained immunity genes, and glycolysis genes; and 6) Gene KO transcriptomes indicated that ATF6 and PERK played more significant roles than IRE1 in promoting AAA and trained immunity whereas antioxidant NRF2 inhibited them. Our unprecedented ER-focused transcriptomic analyses have provided novel insights on the roles of ER as an immune organelle in sensing various DAMPs and initiating ER stress that triggers Ang II-accelerated trained immunity and differs susceptibilities of thoracic and abdominal aortas to diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1268916/fullAng IIER stressmetabolic reprogrammingvascular inflammationtrained immunity |
spellingShingle | Yifan Lu Yu Sun Fatma Saaoud Ying Shao Keman Xu Xiaohua Jiang Xiaohua Jiang Sheng Wu Jun Yu Nathaniel W. Snyder Ling Yang Xinghua Mindy Shi Huaqing Zhao Hong Wang Xiaofeng Yang Xiaofeng Yang ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development Frontiers in Immunology Ang II ER stress metabolic reprogramming vascular inflammation trained immunity |
title | ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development |
title_full | ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development |
title_fullStr | ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development |
title_full_unstemmed | ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development |
title_short | ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development |
title_sort | er stress mediates angiotensin ii augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development |
topic | Ang II ER stress metabolic reprogramming vascular inflammation trained immunity |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1268916/full |
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