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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2018

Open Access 01-12-2018 | Original investigation

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

Authors: Beibei Dai, Huaping Li, Jiahui Fan, Yanru Zhao, Zhongwei Yin, Xiang Nie, Dao Wen Wang, Chen Chen

Published in: Cardiovascular Diabetology | Issue 1/2018

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Abstract

Background

Diabetes is a leading cause of mortality and morbidity across the world. Over 50% of deaths among diabetic patients are caused by cardiovascular diseases. Cardiac diastolic dysfunction is one of the key early signs of diabetic cardiomyopathy, which often occurs before systolic dysfunction. However, no drug is currently licensed for its treatment.

Methods

Type 9 adeno-associated virus combined with cardiac Troponin T promoter were employed to manipulate miR-21 expression in the leptin receptor-deficient (db/db) mice. Cardiac structure and functions were measured by echocardiography and hemodynamic examinations. Primary cardiomyocytes and cardiomyocyte cell lines were used to perform gain/loss-of-function assays in vitro.

Results

We observed a significant reduction of miR-21 in the diastolic dysfunctional heart of db/db mice. Remarkably, delivery of miR-21 efficiently protected against the early impairment in cardiac diastolic dysfunction, represented by decreased ROS production, increased bioavailable NO and relieved diabetes-induced cardiomyocyte hypertrophy in db/db mice. Through bioinformatic analysis and Ago2 co-immunoprecipitation, we identified that miR-21 directly targeted gelsolin, a member of the actin-binding proteins, which acted as a transcriptional cofactor in signal transduction. Moreover, down-regulation of gelsolin by siRNA also attenuated the early phase of diabetic cardiomyopathy.

Conclusion

Our findings reveal a new role of miR-21 in attenuating diabetic cardiomyopathy by targeting gelsolin, and provide a molecular basis for developing a miRNA-based therapy against diabetic cardiomyopathy.
Appendix
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Metadata
Title
MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin
Authors
Beibei Dai
Huaping Li
Jiahui Fan
Yanru Zhao
Zhongwei Yin
Xiang Nie
Dao Wen Wang
Chen Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2018
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-018-0767-z

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