PMID- 35378826
OWN - NLM
STAT- MEDLINE
DCOM- 20220406
LR  - 20220406
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy 
      through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation 
      and Transcription Activation.
PG  - 3773415
LID - 10.1155/2022/3773415 [doi]
LID - 3773415
AB  - BACKGROUND: Many patients with diabetes die from diabetic cardiomyopathy (DCM); 
      however, effective strategies for the prevention or treatment of DCM have not yet 
      been clarified. METHODS: Leptin receptor-deficient (db/db) mice were treated with 
      either the soluble epoxide hydrolase (sEH) inhibitor AUDA or vehicle alone. A 
      virus carrying Nrf2 shRNA was used to manipulate Nrf2 expression in db/db mice. 
      Cardiac structures and functions were analyzed using echocardiography and 
      hemodynamic examinations. Primary cardiomyocytes cultured under high glucose and 
      high fat (HGHF) conditions were used to conduct in vitro loss-of-function assays 
      after culture in the presence or absence of AUDA (1 muM). Fluorescence 
      microscopy-based detection of mCherry-GFP-LC3 was performed to assess autophagic 
      flux. RESULTS: The sEH inhibitor AUDA significantly attenuated ventricular 
      remodeling and ameliorated cardiac dysfunction in db/db mice. Interestingly, AUDA 
      upregulated Nrf2 expression and promoted its nuclear translocation in db/db mice 
      and the HGHF-treated cardiomyocytes. Additionally, AUDA increased autophagy and 
      decreased apoptosis in db/db mice heart. Furthermore, the administration of AUDA 
      promoted autophagic flux and elevated LC3-II protein level in the presence of 
      bafilomycin A1. However, AUDA-induced autophagy was abolished, and the 
      antiapoptotic effect was partially inhibited upon Nrf2 knockdown. CONCLUSION: Our 
      findings suggest that the sEH inhibitor AUDA attenuates cardiac remodeling and 
      dysfunction in DCM via increasing autophagy and reducing apoptosis, which is 
      relevant to activate Nrf2 signaling pathway.
CI  - Copyright (c) 2022 Qin Fang et al.
FAU - Fang, Qin
AU  - Fang Q
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
AD  - Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological 
      Disorders, Wuhan 430030, China.
FAU - Liu, Xiaohui
AU  - Liu X
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
AD  - Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological 
      Disorders, Wuhan 430030, China.
FAU - Ding, Jie
AU  - Ding J
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
AD  - Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological 
      Disorders, Wuhan 430030, China.
FAU - Zhang, Zhihao
AU  - Zhang Z
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
AD  - Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological 
      Disorders, Wuhan 430030, China.
FAU - Chen, Guangzhi
AU  - Chen G
AUID- ORCID: 0000-0003-2004-1486
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
AD  - Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological 
      Disorders, Wuhan 430030, China.
FAU - Du, Tingyi
AU  - Du T
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
AD  - Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological 
      Disorders, Wuhan 430030, China.
FAU - Wang, Yan
AU  - Wang Y
AUID- ORCID: 0000-0003-2046-7604
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
AD  - Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological 
      Disorders, Wuhan 430030, China.
FAU - Xu, Renfan
AU  - Xu R
AUID- ORCID: 0000-0003-1574-5833
AD  - Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430030, China.
LA  - eng
PT  - Journal Article
DEP - 20220325
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Autophagy
MH  - *Diabetes Mellitus
MH  - *Diabetic Cardiomyopathies/metabolism
MH  - Epoxide Hydrolases/genetics/metabolism
MH  - Humans
MH  - Mice
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Transcriptional Activation
MH  - Up-Regulation
PMC - PMC8976467
COIS- The authors declared no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2022/04/06 06:00
MHDA- 2022/04/07 06:00
PMCR- 2022/03/25
CRDT- 2022/04/05 05:11
PHST- 2021/10/17 00:00 [received]
PHST- 2022/02/03 00:00 [revised]
PHST- 2022/02/22 00:00 [accepted]
PHST- 2022/04/05 05:11 [entrez]
PHST- 2022/04/06 06:00 [pubmed]
PHST- 2022/04/07 06:00 [medline]
PHST- 2022/03/25 00:00 [pmc-release]
AID - 10.1155/2022/3773415 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Mar 25;2022:3773415. doi: 10.1155/2022/3773415. 
      eCollection 2022.