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TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance
Joint Authors
Wu, Bang-wei
Li, Jian
Ni, Huanchun
Zhuang, Xinyu
Qi, Zhiyong
Chen, Qiying
Wen, Zhichao
Shi, Haiming
Luo, Xinping
Jin, Bo
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-06-26
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Mitochondrial dynamic imbalance associates with several cardiovascular diseases.
However, the role of mitochondrial dynamics in TLR4 activation-mediated dilated cardiomyopathy (DCM) progress remains unknown.
A model of experimental autoimmune myocarditis (EAM) was established in BALB/c mice on which TLR4 activation by LPS-EB or TLR4 inhibition by LPS-RS was performed to induce chronic inflammation for 5 weeks.
TLR4 activation promoted the transition of EAM to DCM as demonstrated by increased cardiomyocyte apoptosis, myocardial fibrosis, ventricular dilatation, and declined heart function.
TLR4 inhibition mitigated the above DCM changes.
Transmission electron microscope study showed that mitochondria became fragmented, also with damaged crista in ultrastructure in EAM mice.
TLR4 activation aggravated the above mitochondrial aberration, and TLR4 inhibition alleviated it.
The mitochondrial dynamic imbalance and damage in DCM development were mainly associated with OPA1 downregulation, which may be caused by elevated TNF-α level and ROS stress after TLR4 activation.
Furthermore, OMA1/YME1L abnormal degradation was involved in the OPA1 dysfunction, and intervening OMA1/YME1L in H9C2 significantly alleviated mitochondrial fission, ultrastructure damage, and cell apoptosis induced by TNF-α and ROS.
These data indicate that TLR4 activation resulted in OPA1 dysfunction, promoting mitochondrial dynamic imbalance and damage, which may involve in the progress of EAM to DCM.
American Psychological Association (APA)
Wu, Bang-wei& Li, Jian& Ni, Huanchun& Zhuang, Xinyu& Qi, Zhiyong& Chen, Qiying…[et al.]. 2018. TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1211185
Modern Language Association (MLA)
Wu, Bang-wei…[et al.]. TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-15.
https://search.emarefa.net/detail/BIM-1211185
American Medical Association (AMA)
Wu, Bang-wei& Li, Jian& Ni, Huanchun& Zhuang, Xinyu& Qi, Zhiyong& Chen, Qiying…[et al.]. TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1211185
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211185