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Trimetazidine Attenuates Cardiac Dysfunction in Endotoxemia and Sepsis by Promoting Neutrophil Migration

Overview of attention for article published in Frontiers in immunology, September 2018
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Title
Trimetazidine Attenuates Cardiac Dysfunction in Endotoxemia and Sepsis by Promoting Neutrophil Migration
Published in
Frontiers in immunology, September 2018
DOI 10.3389/fimmu.2018.02015
Pubmed ID
Authors

Jing Chen, Bei Wang, Jinsheng Lai, Zachary Braunstein, Mengying He, Guoran Ruan, Zhongwei Yin, Jin Wang, Katherine Cianflone, Qin Ning, Chen Chen, Dao Wen Wang

Abstract

Aims: Cardiac dysfunction can be a fatal complication during severe sepsis. The migration of neutrophils is significantly impaired during severe sepsis. We sought to determine the role of trimetazidine (TMZ) in regulation of neutrophil migration to the heart in a mouse model of sepsis and endotoxemia, and to identify the mechanism whereby TMZ confers a survival advantage. Methods and Results: C57/BL6 mice were (1) injected with LPS followed by 24-h TMZ administration, or (2) treated with TMZ (20 mg/kg/day) for 1 week post cecal ligation and puncture (CLP) operation. Echocardiography and Millar system detection showed that TMZ alleviated cardiac dysfunction and histological staining showed the failure of neutrophils migration to heart in both LPS- and CLP-induced mice. Bone marrow transplantation revealed that TMZ-pretreated bone marrow cells improved LPS- and CLP-induced myocardial dysfunction and enhanced neutrophil recruitment in heart. In CXCL2-mediated chemotaxis assays, TMZ increased neutrophils migration via AMPK/Nrf2-dependent up-regulation of CXCR2 and inhibition of GRK2. Furthermore, using luciferase reporter gene and chromatin immunoprecipitation assays, we found that TMZ promoted the binding of the Nrf2 and CXCR2 promoter regions directly. Application of CXCR2 inhibitor completely reversed the protective effects of TMZ in vivo. Co-culture of neutrophils and cardiomyocytes further validated that TMZ decreased LPS-induced cardiomyocyte pyroptosis by targeting neutrophils. Conclusion: Our findings suggested TMZ as a potential therapeutic agent for septic or endotoxemia associated cardiac dysfunction in mice. STUDY HIGHLIGHTS  What is the current knowledge on the topic? Migration of neutrophils is significantly impaired during severe sepsis, but the underlying mechanisms remain unknown. What question did this study address? The effects of TMZ on cardiac dysfunction via neutrophils migration. What this study adds to our knowledge TMZ attenuated LPS-induced cardiomyocyte pyroptosis and cardiac dysfunction by promoting neutrophils recruitment to the heart tissues via CXCR2. How this might change clinical pharmacology or translational science Our findings suggested TMZ as a potential therapeutic agent for septic cardiac dysfunction.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 17%
Other 3 10%
Researcher 3 10%
Student > Ph. D. Student 3 10%
Student > Doctoral Student 2 7%
Other 4 13%
Unknown 10 33%
Readers by discipline Count As %
Medicine and Dentistry 7 23%
Biochemistry, Genetics and Molecular Biology 5 17%
Immunology and Microbiology 3 10%
Agricultural and Biological Sciences 2 7%
Decision Sciences 1 3%
Other 3 10%
Unknown 9 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 September 2018.
All research outputs
#20,755,951
of 25,498,750 outputs
Outputs from Frontiers in immunology
#24,934
of 31,842 outputs
Outputs of similar age
#268,956
of 345,566 outputs
Outputs of similar age from Frontiers in immunology
#519
of 638 outputs
Altmetric has tracked 25,498,750 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,842 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 345,566 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 638 others from the same source and published within six weeks on either side of this one. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.