ArticleCell reports. Medicine2025
Targeting USP21 to inhibit abdominal aortic aneurysm progression by suppressing the phenotypic transition of vascular smooth muscle cells.
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Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- DTX1 Regulates Aortic Dissection Progression by Modulating Vascular Smooth Muscle Cell Phenotypic Switching via Ubiquitination of ITGA5.Cardiovascular drugs and therapy · 2026Article
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13 authors.
Huidan ZhangDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Hongwei YueDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Yijun SunDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Guangqi SunDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Kehui YangDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Tangxing JiangDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Sumei CuiDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Yang LiuDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Yunyun GuoDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Wencheng ZhangNational Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Cheng ZhangNational Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China.
Yuguo ChenDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: chen919085@sdu.edu.cn.
Feng XuDepartment of Emergency Medicine, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, China; Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan 250012, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: xufengsdu@126.com.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abdominal aortic aneurysm (AAA) is a life-threatening condition lacking effective treatment. We investigate the role of the deubiquitinating enzyme USP21 in AAA development. Proteomic analysis reveals significant upregulation of USP21 in murine and human abdominal aortic tissues. Using USP21 global knockout models induced by angiotensin II or porcine pancreatic elastase (PPE), and vascular smooth muscle cell (VSMC)-specific models, we assess USP21's impact on AAA. Coimmunoprecipitation and mass spectrometry identify downstream targets of USP21. USP21 exacerbates AAA by stabilizing aldehyde dehydrogenase 2 (ALDH2) and promoting VSMC dedifferentiation and phenotypic changes. Pharmacological inhibition of USP21 with disulfiram shows therapeutic potential against AAA progression, with efficacy reduced in ALDH2
Indexed as
Aortic Aneurysm, AbdominalMuscle, Smooth, VascularMyocytes, Smooth MuscleUbiquitin ThiolesteraseAldehyde Dehydrogenase, MitochondrialAngiotensin IIAnimalsDisease Models, AnimalDisease ProgressionHumansMaleMiceMice, Inbred C57BLMice, KnockoutPhenotypeAldehyde Dehydrogenase, MitochondrialAngiotensin IIUbiquitin Thiolesteraseabdominal aortic aneurysmaldehyde dehydrogenase 2deubiquitinating enzymesUSP21VSMC phenotypic switch
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