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The Impact of Circulating Mitochondrial DNA on Cardiomyocyte Apoptosis and Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis.
Cell Physiol Biochem. 2017; 42(2):713-728.CP

Abstract

BACKGROUND/AIMS

Mitochondrial DNA (mtDNA), acting as a newly found 'danger-associated molecular patterns' (DAMPs), is released into circulation upon tissue injury and performs as a considerable activator of inflammation and immune response. However, the role of circulating mtDNA in experimental autoimmune myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac inflammation and injury remains unknown.

METHODS

A model of EAM was established in BALB/c mice by immunization with porcine cardiac myosin. Lipopolysaccharide (LPS) was used to stimulate TLR4 activation in EAM mice and H9C2 cells.

RESULTS

LPS stimulation significantly aggravated cardiac inflammation and tissue injury in EAM, as demonstrated by increased myocardium inflammatory cell infiltration, and up-regulated inflammatory cytokines and troponin I(TnI) level in serum. Circulating mtDNA level was increased in EAM and TLR4 activation led to a greater elevation, which may be related to Reactive oxygen species (ROS) stress involved mtDNA damage characterized by reduced mtDNA copy number in myocardium tissue. In addition, the expression of Toll like receptor9 (TLR9), a ligand of mtDNA, was significantly up-regulated in the myocardium of EAM and EAM LPS group; meanwhile, TLR9 inhibition by ODN 2088 caused an inhibited apoptosis in LPS treated H9C2 cells. Moreover, in EAM and EAM LPS group, simultaneously giving ODN 2088 treatment significantly ameliorated cardiac inflammation and tissue injury compared with untreated group.

CONCLUSION

Increased circulating mtDNA combined with upregulated TLR9 expression may corporately play a role in EAM as well as TLR4 activation mediated cardiac inflammation and injury.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

28618428

Citation

Wu, Bangwei, et al. "The Impact of Circulating Mitochondrial DNA On Cardiomyocyte Apoptosis and Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 42, no. 2, 2017, pp. 713-728.
Wu B, Ni H, Li J, et al. The Impact of Circulating Mitochondrial DNA on Cardiomyocyte Apoptosis and Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis. Cell Physiol Biochem. 2017;42(2):713-728.
Wu, B., Ni, H., Li, J., Zhuang, X., Zhang, J., Qi, Z., Chen, Q., Wen, Z., Shi, H., Luo, X., & Jin, B. (2017). The Impact of Circulating Mitochondrial DNA on Cardiomyocyte Apoptosis and Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 42(2), 713-728. https://doi.org/10.1159/000477889
Wu B, et al. The Impact of Circulating Mitochondrial DNA On Cardiomyocyte Apoptosis and Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis. Cell Physiol Biochem. 2017;42(2):713-728. PubMed PMID: 28618428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Impact of Circulating Mitochondrial DNA on Cardiomyocyte Apoptosis and Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis. AU - Wu,Bangwei, AU - Ni,Huanchun, AU - Li,Jian, AU - Zhuang,Xinyu, AU - Zhang,Jinjin, AU - Qi,Zhiyong, AU - Chen,Qiying, AU - Wen,Zhichao, AU - Shi,Haiming, AU - Luo,Xinping, AU - Jin,Bo, Y1 - 2017/06/15/ PY - 2016/12/01/received PY - 2017/04/13/accepted PY - 2017/6/16/pubmed PY - 2017/8/5/medline PY - 2017/6/16/entrez KW - Circulating mtDNA KW - EAM KW - ROS stress KW - TLR4 KW - TLR9 SP - 713 EP - 728 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 42 IS - 2 N2 - BACKGROUND/AIMS: Mitochondrial DNA (mtDNA), acting as a newly found 'danger-associated molecular patterns' (DAMPs), is released into circulation upon tissue injury and performs as a considerable activator of inflammation and immune response. However, the role of circulating mtDNA in experimental autoimmune myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac inflammation and injury remains unknown. METHODS: A model of EAM was established in BALB/c mice by immunization with porcine cardiac myosin. Lipopolysaccharide (LPS) was used to stimulate TLR4 activation in EAM mice and H9C2 cells. RESULTS: LPS stimulation significantly aggravated cardiac inflammation and tissue injury in EAM, as demonstrated by increased myocardium inflammatory cell infiltration, and up-regulated inflammatory cytokines and troponin I(TnI) level in serum. Circulating mtDNA level was increased in EAM and TLR4 activation led to a greater elevation, which may be related to Reactive oxygen species (ROS) stress involved mtDNA damage characterized by reduced mtDNA copy number in myocardium tissue. In addition, the expression of Toll like receptor9 (TLR9), a ligand of mtDNA, was significantly up-regulated in the myocardium of EAM and EAM LPS group; meanwhile, TLR9 inhibition by ODN 2088 caused an inhibited apoptosis in LPS treated H9C2 cells. Moreover, in EAM and EAM LPS group, simultaneously giving ODN 2088 treatment significantly ameliorated cardiac inflammation and tissue injury compared with untreated group. CONCLUSION: Increased circulating mtDNA combined with upregulated TLR9 expression may corporately play a role in EAM as well as TLR4 activation mediated cardiac inflammation and injury. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/28618428/The_Impact_of_Circulating_Mitochondrial_DNA_on_Cardiomyocyte_Apoptosis_and_Myocardial_Injury_After_TLR4_Activation_in_Experimental_Autoimmune_Myocarditis_ L2 - https://www.karger.com?DOI=10.1159/000477889 DB - PRIME DP - Unbound Medicine ER -