MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin
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 dy...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2018-09-01
|
Series: | Cardiovascular Diabetology |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12933-018-0767-z |
id |
doaj-4d8d41f725af46b6afb3fb06fc8df939 |
---|---|
record_format |
Article |
spelling |
doaj-4d8d41f725af46b6afb3fb06fc8df9392020-11-25T00:25:02ZengBMCCardiovascular Diabetology1475-28402018-09-0117111710.1186/s12933-018-0767-zMiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolinBeibei Dai0Huaping Li1Jiahui Fan2Yanru Zhao3Zhongwei Yin4Xiang Nie5Dao Wen Wang6Chen Chen7Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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.http://link.springer.com/article/10.1186/s12933-018-0767-zmiRNADiabetic cardiomyopathyDiastolic dysfunctionROSNO |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Beibei Dai Huaping Li Jiahui Fan Yanru Zhao Zhongwei Yin Xiang Nie Dao Wen Wang Chen Chen |
spellingShingle |
Beibei Dai Huaping Li Jiahui Fan Yanru Zhao Zhongwei Yin Xiang Nie Dao Wen Wang Chen Chen MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin Cardiovascular Diabetology miRNA Diabetic cardiomyopathy Diastolic dysfunction ROS NO |
author_facet |
Beibei Dai Huaping Li Jiahui Fan Yanru Zhao Zhongwei Yin Xiang Nie Dao Wen Wang Chen Chen |
author_sort |
Beibei Dai |
title |
MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin |
title_short |
MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin |
title_full |
MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin |
title_fullStr |
MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin |
title_full_unstemmed |
MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin |
title_sort |
mir-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin |
publisher |
BMC |
series |
Cardiovascular Diabetology |
issn |
1475-2840 |
publishDate |
2018-09-01 |
description |
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. |
topic |
miRNA Diabetic cardiomyopathy Diastolic dysfunction ROS NO |
url |
http://link.springer.com/article/10.1186/s12933-018-0767-z |
work_keys_str_mv |
AT beibeidai mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin AT huapingli mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin AT jiahuifan mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin AT yanruzhao mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin AT zhongweiyin mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin AT xiangnie mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin AT daowenwang mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin AT chenchen mir21protectedagainstdiabeticcardiomyopathyinduceddiastolicdysfunctionbytargetinggelsolin |
_version_ |
1725350182060556288 |