Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis
Thoracic aortic aneurysm/dissection (TAAD) is a severe vascular condition associated with life-threatening complications, and its underlying molecular mechanisms remain largely unexplored. Previous research indicates that the aberrant activation of cytosolic DNA and its receptors plays a crucial rol...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Extracellular Vesicle |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773041724000131 |
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| author | Lin Lu Feng Liu Weiliang Wu Yu Zhang Bin Liu Qingfang Han Tonggan Lu Huiling Zhang Xi-yong Yu Yangxin Li |
| author_facet | Lin Lu Feng Liu Weiliang Wu Yu Zhang Bin Liu Qingfang Han Tonggan Lu Huiling Zhang Xi-yong Yu Yangxin Li |
| author_sort | Lin Lu |
| collection | DOAJ |
| description | Thoracic aortic aneurysm/dissection (TAAD) is a severe vascular condition associated with life-threatening complications, and its underlying molecular mechanisms remain largely unexplored. Previous research indicates that the aberrant activation of cytosolic DNA and its receptors plays a crucial role in vascular inflammation and dysfunction. Specifically, Absent in Melanoma 2 (AIM2), an intracellular DNA receptor, can trigger the inflammasome pathway, leading to extracellular matrix destruction. In this investigation, we delved into the mechanism underlying AIM2 activation in TAAD development and explored the potential of exosomes to impede TAAD progression by suppressing AIM2 expression. Our findings revealed that heightened AIM2 expression and activation contribute to TAAD development by fostering vascular inflammation and disrupting vascular homeostasis. Activated AIM2 induces pyroptosis through the recruitment of the deubiquitination enzyme USP21, which stabilizes AIM2 by reducing its ubiquitination and degradation. Moreover, we demonstrated that exosome-derived miR-485-5p exerts an anti-inflammatory and protective effect on the thoracic aorta by inhibiting AIM2 activation. This study introduces novel perspectives for the treatment of TAAD. |
| format | Article |
| id | doaj-art-ea6ce1da2f2f4ee38d03320e67e5e8b4 |
| institution | Kabale University |
| issn | 2773-0417 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Extracellular Vesicle |
| spelling | doaj-art-ea6ce1da2f2f4ee38d03320e67e5e8b42024-12-19T11:03:19ZengElsevierExtracellular Vesicle2773-04172024-12-014100046Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosisLin Lu0Feng Liu1Weiliang Wu2Yu Zhang3Bin Liu4Qingfang Han5Tonggan Lu6Huiling Zhang7Xi-yong Yu8Yangxin Li9Institute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR ChinaInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR ChinaInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR ChinaInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR ChinaDepartment of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, PR ChinaInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR ChinaInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR ChinaInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR ChinaKey Laboratory of Molecular Target & Clinical Pharmacology and the NMPA & State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, 511436, PR ChinaInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215123, PR China; Corresponding author. Institute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215123, PR China.Thoracic aortic aneurysm/dissection (TAAD) is a severe vascular condition associated with life-threatening complications, and its underlying molecular mechanisms remain largely unexplored. Previous research indicates that the aberrant activation of cytosolic DNA and its receptors plays a crucial role in vascular inflammation and dysfunction. Specifically, Absent in Melanoma 2 (AIM2), an intracellular DNA receptor, can trigger the inflammasome pathway, leading to extracellular matrix destruction. In this investigation, we delved into the mechanism underlying AIM2 activation in TAAD development and explored the potential of exosomes to impede TAAD progression by suppressing AIM2 expression. Our findings revealed that heightened AIM2 expression and activation contribute to TAAD development by fostering vascular inflammation and disrupting vascular homeostasis. Activated AIM2 induces pyroptosis through the recruitment of the deubiquitination enzyme USP21, which stabilizes AIM2 by reducing its ubiquitination and degradation. Moreover, we demonstrated that exosome-derived miR-485-5p exerts an anti-inflammatory and protective effect on the thoracic aorta by inhibiting AIM2 activation. This study introduces novel perspectives for the treatment of TAAD.http://www.sciencedirect.com/science/article/pii/S2773041724000131AIM2Thoracic aortic aneurysm/dissectionInflammationDeubiquitinating enzymesExosome |
| spellingShingle | Lin Lu Feng Liu Weiliang Wu Yu Zhang Bin Liu Qingfang Han Tonggan Lu Huiling Zhang Xi-yong Yu Yangxin Li Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis Extracellular Vesicle AIM2 Thoracic aortic aneurysm/dissection Inflammation Deubiquitinating enzymes Exosome |
| title | Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis |
| title_full | Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis |
| title_fullStr | Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis |
| title_full_unstemmed | Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis |
| title_short | Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis |
| title_sort | stem cell derived exosomes prevent the development of thoracic aortic aneurysm dissection by inhibiting aim2 inflammasome and pyroptosis |
| topic | AIM2 Thoracic aortic aneurysm/dissection Inflammation Deubiquitinating enzymes Exosome |
| url | http://www.sciencedirect.com/science/article/pii/S2773041724000131 |
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